Skip to main content
Log in

Growth Factors in Glioma Angiogenesis: FGFs, PDGF, EGF, and TGFs

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

It has become well accepted that solid tumors must create a vascular system for nutrient delivery and waste removal in order to grow appreciably. This process, angiogenesis, is critical to the progression of gliomas, with vascular changes accompanying the advancement of these tumors. The cascade of events in this process of blood vessel formation involves a complex interplay between tumor cells, endothelial cells, and their surrounding basement membranes in which enzymatic degradation of surrounding ground substance and subsequent endothelial cell migration, proliferation, and tube formation occurs. It is likely that a host of growth factors is responsible for mediating these key events. To date, a role for Vascular Endothelial Growth Factor (VEGF) in glioma angiogenesis has been convincingly demonstrated. This review explores the contribution of other growth factors–-Fibroblast Growth Factors (FGFs), Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), and Transforming Growth Factors (TGFs)–-to glioma angiogenesis. These growth factors may influence glioma angiogenesis by directly stimulating endothelial cell proliferation, by mediating the expression of key proteases on endothelial cells necessary for angiogenesis, or by regulating the expression of VEGF and of each other.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cavallo T, Sade R, Folkman J, Cotran RS: Tumor angiogenesis. Rapid induction of endothelial mitoses demonstrated by autoradiography. J Cell Biol 54: 408-20, 1972

    Google Scholar 

  2. Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442-7, 1987

    Google Scholar 

  3. Folkman J: What is the evidence that tumors are angiogenesis dependent? J Nat Cancer Inst 82: 4-6, 1990

    Google Scholar 

  4. Gough J: The structure of the blood vessels in cerebral tumors. J Pathol Bacteriol 51: 23-8, 1940

    Google Scholar 

  5. Feigin I, Allen LB, Gross SW: The endothelial hyperplasia of the cerebral blood vessels with brain tumors and its sarcomatous transformation. Cancer 11: 265-77, 1958

    Google Scholar 

  6. Nystron S: Pathological changes in blood vessels of human glioblastoma multiforme. Comparative study using plastic coating angiography with reference to some other brain tumors. Acta Pathol Microbiol Scan 49: 1083, 1960

    Google Scholar 

  7. Burger PC, Vogel FS, Green SB, Strike TA: Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer 56: 1106-11, 1985

    Google Scholar 

  8. Daumas-Duport C, Scheithauer BW, O'Fallon J, Kelly PJ: Grading of astrocytomas: a simple and reproducible method. Cancer 62: 2152-65, 1988

    Google Scholar 

  9. Long DM: Capillary ultrastructure and the blood-brain barrier in human malignant brain tumors. J Neurosurg 32: 127-44, 1970

    Google Scholar 

  10. Weller RO, Foy M, Cox S: The development and ultrastructure of the microvasculature in malignant gliomas. Neuropathol Appl Neurobiol 3: 307-22, 1977

    Google Scholar 

  11. Leon SP, Folkerth RD, Black PM: Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77: 362-72, 1996

    Google Scholar 

  12. Ito M, Lammertsma AA, Wise RJ, Bernardi S, Frackowiak RS, Heather JD, McKenzie CG, Thomas DG, Jones T: Measurement of regional cerebral blood flow and oxygen utilisation in patients with cerebral tumours using 15O and positron emission tomography: analytical techniques and preliminary results. Neuroradiology 23: 63-74, 1982

    Google Scholar 

  13. Kaye A, Laws E (ed) Brain tumors: an encyclopedic approach. New York, Churchill Livingstone, 1995

    Google Scholar 

  14. Liwnicz BH, Wu SZ, Tew JM: The relationship between the capillary structure and hemorrhage in gliomas. J Neurosurg 66: 536-41, 1987

    Google Scholar 

  15. Klagsbrun M, Folkman J: Angiogenesis. In: Sporn MB, Roberts AB (eds) Peptide growth factors and their receptors. New York, Springer, 1990, pp 549-86

    Google Scholar 

  16. De Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT: The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255: 989-91, 1992

    Google Scholar 

  17. Terman BI, Dougher-Vermazen M, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, Bohlen P: Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 187: 1579-86, 1992

    Google Scholar 

  18. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M: Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92: 735-45, 1998

    Google Scholar 

  19. Senger DR, Galli SJ, Dvorak AM, Peruzzi CA, Harvey VS, Dvorak HF: Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219: 983-5, 1983

    Google Scholar 

  20. Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246: 1309-12, 1989

    Google Scholar 

  21. Connolly DT, Heuvelman DM, Nelson R, Olander JV, Eppley BL, Delfino JJ, Siegel NR, Leimgruber RM, Feder J: Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 84: 1470-8, 1989

    Google Scholar 

  22. Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359: 845-8, 1992

    Google Scholar 

  23. Jaye M, Howk R, Burgess W, Ricca GA, Chiu I-M, Ravera MW, O'Brien SJ, Modi WS, Maciag T, Drohan WN: Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science 233: 541-5, 1986

    Google Scholar 

  24. Abraham JA, Whang JL, Tumolo A, Mergia A, Fiddes JC: Human basic fibroblast growth factor: nucleotide sequence, genomic organization, and expression in mammalian cells. Cold Spring Harbor Symp Quant Biol 51: 657-68, 1986a

    Google Scholar 

  25. Abraham JA, Mergia A, Whang JL, Tumolo A, Friedman J, Hjerrild KA, Gospodarowicz D, Fiddes JC: Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science 233: 545-8, 1986b

    Google Scholar 

  26. Dickson C, Smith R, Brookes S, Peters G: Tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2. Cell 37: 529-36, 1984

    Google Scholar 

  27. Sakamoto H, Mori M, Taira M, Yoshida T, Matsukawa S, Shimizu K, Sekiguchi M, Terada M, Sugimura T: Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa. Proc Natl Acad Sci USA 83: 3997-4001, 1986

    Google Scholar 

  28. Yoshida MC, Wada M, Satoh H, Yoshida T, Sakamoto H, Miyagawa K, Yokota J, Koda T, Kakinuma M, Sugimura T: Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer. Proc Natl Acad Sci USA 85: 4861-4, 1988

    Google Scholar 

  29. Zhan X, Bates B, Hu XG, Goldfarb M: The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors. Mol Cell Biol 8: 3487-95, 1988

    Google Scholar 

  30. Marics I, Adelaide J, Raybaud F, Matteio MG, Coulier F, Planche J, de Lapeyriere O, Birnbaum D: Characterization of the HST-related FGF-6 gene, a new member of the fibroblast growth factor family. Oncogene 4: 335-40, 1989

    Google Scholar 

  31. Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA: Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 86: 802-6, 1989

    Google Scholar 

  32. Tanaka A, Miyamoto K, Minamino HN, Takeda M, Sato B, Matsuo H, Matsumoto K: Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells. Proc Natl Acad Sci USA 89: 8928-32, 1992

    Google Scholar 

  33. Miyamoto M, Nauro K, Seko C, Matsukmoto S, Kondo T, Kurokawa T: Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. Mol Cell Biol 13: 4251-9, 1993

    Google Scholar 

  34. Yamasaki M, Miyake A, Tagashira S, Itoh N: Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family. J Biol Chem 271: 15918-21, 1996

    Google Scholar 

  35. Hartung H, Feldman B, Lovec H, Coulier F, Birnbaum D, Goldfarb M: Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue, and heart. Mech Dev 64: 31-9, 1997

    Google Scholar 

  36. Liu Y, Chiu IM: Assignment of FGF12, the human FGF homologous factor 1 gene, to chromosome 3q29-3qter by fluorescence in situ hybridization. Cytogenet Cell Genet 78: 48-9, 1997

    Google Scholar 

  37. Greene HM, Li YL, Yourey PA, Gruber J, Carter KC, Shell BK, Dillon PA, Florence C, Duan DR, Blunt A, Ornitz DM, Ruben SM, Alderson RF: Identification and characterization of a novel member of the fibroblast growth factor family. Eur J Neurosci 10: 1911-25, 1998

    Google Scholar 

  38. McWhirter JR, Goulding M, Weiner JA, Chun J, Murre C: A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1. Development 124: 3221-32, 1997

    Google Scholar 

  39. Miyake A, Konishe M, Martin FH, Hernday NA, Ozaki K, Yamamoto S, Mikami T, Arakawa T, Itoh N: Structure and expression of a novel member, FGF-16, on the fibroblast growth factor family. Biochem Biophys Res Commun 243: 148-52, 1998

    Google Scholar 

  40. Hoshikawa M, Ohbayashi N, Yonamine A, Konishi M, Ozaki K, Fukui S, Itoh N: Structure and expression of a novel fibroblast growth factor, FGF-17, preferentially expressed in the embryonic brain. Biochem Biophys Res Commun 244: 187-91, 1998

    Google Scholar 

  41. Ohbayashi N, Hoshikawa M, Kimura S, Yamasaki M, Fukui S, Itoh N: Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF-18. J Biol Chem 273: 18161-4, 1998

    Google Scholar 

  42. Nishimura T, Utsunomiya Y, Hoshikawa M, Ohuchi H, Itoh N: Structure and expression of a novel human FGF, FGF-19, expressed in the fetal brain. Biochim Biophys Acta 1444: 148-51, 1999

    Google Scholar 

  43. Klagsbrun M: The fibroblast growth factor family: structural and biological properties. Prog Growth Factor Res 1: 207-35, 1989

    Google Scholar 

  44. Klagsbrun M, D'Amore P: Regulators of angiogenesis. Annu Rev Physiol 53: 217-39, 1991

    Google Scholar 

  45. Klein S, Roghani M, Rifkin DB: Fibroblast growth factors as angiogenesis factors: new insights into their mechanism of action. EXS 79: 159-92, 1997

    Google Scholar 

  46. Bikfalvi A, Klein S, Pintucci G, Rifkin DB: Biological roles of fibroblast growth factor-2. Endocr Rev 18: 26-45, 1997

    Google Scholar 

  47. Lafage-Pochitaloff M, Galland F, Simonetti J, Prats H, Mattei MG, Birnbaum D: The human basic fibroblast growth factor gene is located on the long arm of chromosome 4 at bands q26-q27. Oncogene Res 5: 241-4, 1990

    Google Scholar 

  48. Fukushima Y, Byers MG, Fiddes JC, Shows TB: The human fibroblast growth factor gene (FGFB) is assigned to chromosome 4q25. Cytogenet Cell Genet 54: 159-60, 1990

    Google Scholar 

  49. Florkiewicz RZ, Baird A: Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc Natl Acad Sci USA 86: 3978-81, 1989

    Google Scholar 

  50. Prats H, Kaghad M, Prats AC, Klagsbrun M, Lelias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA, Caput D: High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci USA 86: 1836-40, 1989

    Google Scholar 

  51. Florkiewicz RZ, Majack RA, Buechler RD, Florkiewicz E: Quantitative export of FGF-2 occurs through an alternative, energy-dependent, non-ER/Golgi pathway. J Cell Physiol 162: 388-99, 1995

    Google Scholar 

  52. Mignatti P, Morimoto T, Rifkin DB: Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol 151: 81-93, 1992

    Google Scholar 

  53. Lee PL, Johnson DE, Cousens LS, Fried VA, Williams LT: Purification and complementary DNA of a receptor for basic fibroblast growth factor. Science 245: 57-60, 1989

    Google Scholar 

  54. Dionne CA, Crumley G, Bellot F, Kaplow JM, Searfoss G, Ruta M, Burgess WH, Jaye M, Schlessinger J: Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J 9: 2685-92, 1990

    Google Scholar 

  55. Keegan K, Johnson DE, Williams LT, Hayman JF: Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3. Proc Natl Acad Sci USA 88: 1095-9, 1991

    Google Scholar 

  56. Partanen J, Makela TP, Eerola E, Korhonen J, Hirvonen H, Claesson-Welsh L, Alitalo K: FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. EMBO J 10: 1347-54, 1991

    Google Scholar 

  57. Basilico C, Moscatelli D: The FGF family of growth factors and oncogenes. Adv Cancer Res 59: 115-65, 1992

    Google Scholar 

  58. Jaye M, Schlessinger J, Dionne C: Fibroblast growth factor receptor for acidic and basic fibroblast growth factors. Biochim Biophys Acta 1135: 185-99, 1992

    Google Scholar 

  59. Lafage M, Pedeutour F, Marchetto S, Simonetti J, Prosperi MT, Gaudray P, Birnbaum D: Fusion and amplification of two originally non-syntenic chromosomal regions in a mammary carcinoma cell line. Genes Chromosomes Cancer 5: 40-9, 1992

    Google Scholar 

  60. Mattei MG, Moreau A, Gesnel MC, Houssaint E, Breathnach R: Assignment by in situ hybridization of a fibroblast growth factor receptor gene to human chromosome band 10q26. Hum Genet 87: 84-6, 1991

    Google Scholar 

  61. Keegan K, Rooke L, Hayman M, Spurr NK: The fibroblast growth factor receptor 3 gene (FGFR3) is assigned to human chromosome 4. Cytogenet Cell Genet 62: 172-5, 1993

    Google Scholar 

  62. Armstrong E, Partanten J, Cannizzaro L, Huebner K, Alitalo K: Localization of the fibroblast growth factor receptor-4 gene to chromosome region 5q33-ter. Genes Chromosomes Cancer 4: 94-8, 1992

    Google Scholar 

  63. Plotnikov AN, Schlessinger J, Hubbard SR, Mohammadi M: Structural basis for FGF receptor dimerization and activation. Cell 98: 641-50, 1999

    Google Scholar 

  64. Ornitz DM, Yayon A, Flanagan JG, Svahn CM, Levi E, Leder P: Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. Mol Cell Biol 12: 240-7, 1992

    Google Scholar 

  65. Folkman J, Klagsbrun M: Angiogenic factors. Science 235: 442-7, 1987

    Google Scholar 

  66. Murphy PR, Sato R, SatoY, Friesen HG: Fibroblast growth factor messenger ribonucleic acid expression in a human astrocytoma cell line: regulation by serum and cell density. Mol Endocrinol 2: 591-8, 1988

    Google Scholar 

  67. Stefanik DF, Rizkalla LR, Soi A, Goldblatt SA, Rizkalla WM: Acidic and basic fibroblast growth factors are present in glioblastoma multiforme. Cancer Res 51: 5760-5, 1991

    Google Scholar 

  68. Zagzag D, Miller DC, Sato Y, Rifkin DB, Burstein DE: Immunohistochemical localization of basic fibroblast growth factor in astrocytomas. Cancer Res 50: 7393-8, 1990

    Google Scholar 

  69. Morrison RS, Yamaguchi F, Saya H, Bruner JM, Yahanda AM, Donehower LA, Berger M: Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas. J Neuro-Oncol 18: 207-16, 1994a

    Google Scholar 

  70. Morrison RS, Yamaguchi F, Bruner JM, Tang M, McKeehan W, Berger MS: Fibroblast growth factor receptor gene expression and immunoreactivity are elevated in human glioblastoma multiforme. Cancer Res 54: 2794-9, 1994b

    Google Scholar 

  71. Ueba T, Takahashi JA, Fukumoto M, Ohta M, Ito N, OdaY, Kikuchi H, Hatanaka M: Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues. Neurosurgery 221-6, 1994

  72. Thomas KA, Gimenez-Gallego G: Fibroblast growth factors: broad spectrum mitogens with potent angiogenic activity. Trends Biochem Sci 11: 81-4, 1986

    Google Scholar 

  73. Thomas KA: Fibroblast growth factors. FASEB J 1: 434-40, 1987

    Google Scholar 

  74. VassaHi JD, Sappino AP, Belin D: The plasminogen activator/plasmin system. J Clin Invest 88: 1067-72, 1991

    Google Scholar 

  75. Mignatti P, Rifkin DB: Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161-95, 1993

    Google Scholar 

  76. Saksela 0, Rifkin DB: Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity. J Cell Biol 110: 767-75, 1990

    Google Scholar 

  77. Blasi F: Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. Bioessays 15: 105-11, 1993

    Google Scholar 

  78. Werb Z, Banda MJ, Jones PA: Degradation of connective tissue matrices by macrophages. Proteolysis of elastin, glycoproteins, and collagen by proteinases isolated from macrophages. J Exp Med 152: 1340-57, 1980

    Google Scholar 

  79. Moscatelli D, Presta M, Rifkin DB:. Purification of a factor from human placenta that stimuary endothelial cell protease production, DNA synthesis, and migration. Proc Natl Acad Sci USA 83: 2091-5, 1986

    Google Scholar 

  80. Mignatti P, Mazzieri R, Rilkin DB: Expression of the urokinase receptor in vascular endothelial cells is stimulated by basic fibroblast growth factor. J Cell Biol 113: 1193-201, 1991

    Google Scholar 

  81. Connolly DT, Stoddard BL, Harakas NK, Feder J: Human fibroblast-derived growth factor is a mitogen and chemoattractant for endothelial cells. Biochem Biophys Res Commun 144: 705-12, 1987

    Google Scholar 

  82. Montesano R, Vassalli JD, Baird A, Guillemin R, Orci L: Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA 83: 7297-301, 1986

    Google Scholar 

  83. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13: 9-22, 1999

    Google Scholar 

  84. Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol 237: 97-132, 1999

    Google Scholar 

  85. Ferrara N: Vascular endothelial growth factor: molecular and biological aspects. Curr Top Microbiol Immunol 237: 1-30, 1999

    Google Scholar 

  86. Plate KH, Breier G, Weich HA, Risau W: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359: 845-8 1992

    Google Scholar 

  87. Tsai JC, Goldman CK, Gillespie GY: Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg 82: 864-73, 1995

    Google Scholar 

  88. Stan AC, Nemati MN, Pietsch T, Walter GF, Dietz H: In vivo inhibition of angiogenesis and growth of the human U-87 malignant glial tumor by treatment with an antibody against basic fibroblast growth factor. J Neurosurg 82: 1044-52, 1995

    Google Scholar 

  89. Abe T, Okamura K, Ono M, Kohno K, Mori T, Hori S, Kuwano M: Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis. J Clin Invest 92: 54-61, 1993

    Google Scholar 

  90. Takahashi JA, Fukumoto M, Igarashi K, Oda Y, Kikuchi H, Hatanaka M: Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas. J Neurosurg 76: 792-8, 1992

    Google Scholar 

  91. Li VW, Folkerth RD, Watanabe H, Yu C, Rupnick M, Barnes P, Scott RM, Black PM, Sallan SE, Folkman J: Microvessel count and cerebrospinal fluid basic fibroblast growth factor in children with brain tumors. Lancet 344: 82-6, 1994

    Google Scholar 

  92. Leon SP, Folkerth RD, Black PM: Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer 77: 367-72, 1996

    Google Scholar 

  93. Bello L, Zhang J, Nikas D, Strasser J, Carroll R, Villani RM, Bikfalvi A, Black PM: FGF-4 as an angiogenesis factor in gliomas. (Abstract) Congress of Neurological Surgeons meeting. Boston Massachusetts October 30-November 4, 1999

  94. Kaplan DR, Chao FC, Stiles CD, Antoniades HN, Scher CD: Platelet alpha granules contain a growth factor for fibroblasts. Blood 53: 1043-52, 1979

    Google Scholar 

  95. Heldin CH, Wasteson A, Westermark B: Platelet-derived growth factor. Mol Cell Endocrinol 39: 169-87, 1985

    Google Scholar 

  96. Antoniades HN: PDGF: a multifunctional growth factor. Baillieres Clin Endocrinol Metab 5: 595-613, 1991

    Google Scholar 

  97. Antoniades HN, Scher CD, Stiles CD: Purification of human platelet-derived growth factor. Proc Natl Acad Sci USA 76: 1809-13, 1979

    Google Scholar 

  98. Heldin CH, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79: 1283-316, 1999

    Google Scholar 

  99. Bowen-Pope DF, Hart CE, Seifert RA: Sera and conditioned media contain different isoforms of platelet derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem 264: 2502-8, 1989

    Google Scholar 

  100. Betsholtz C, Johnsson A, Heldin CH, Westermark B, Lin d P, Urdea MS, Eddy R, Shows TB, Philpott K, Mellor AL, Knott TJ, Scott J: cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature 320: 695-9, 1986

    Google Scholar 

  101. Dalla-Favera R, Gallo RC, Giallonga A, Croce CM: Chromosomal location of the human homolog (c-sis) of the simian sarcoma virus oncogene. Science 218: 686-8, 1982

    Google Scholar 

  102. Bonthron DT, Morton CC, Orkin SH, Collins T: Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc Natl Acad Sci USA 85: 1492-6, 1988

    Google Scholar 

  103. Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN: Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221: 275-7, 1983

    Google Scholar 

  104. Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF: Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304: 35-9, 1983

    Google Scholar 

  105. Swan DC, McBride OW, Robbins KC, Keithley DA, Reddy EP, Aaronson SA: Chromosomal mapping of the simian sarcoma virus onc gene analogue in human cells. Proc Natl Acad Sci USA 79: 4691-5, 1982

    Google Scholar 

  106. Claesson-Welsh L: Signal transduction by the PDGF receptors. Prog Growth Factor Res 5: 37-54, 1994

    Google Scholar 

  107. Gronwald RGK, Grand FJ, Haldeman BA, Hart CE, O'Hara PJ, Hagen FS, Ross R, Bowen-Pope DF, Murray MJ: Cloning and expression of a cDNA cloning for the human platelet-derived growth factor receptor: evidence of more than one receptor class. Proc Natl Acad Sci USA 85: 3435-9, 1988

    Google Scholar 

  108. Hart CE, Forstrom JW, Kelly JD, Seifert RA, Smith RA, Ross R, Murray MJ, Bowen-Pope DF: Two classes of PDGF receptor recognize different isoforms of PDGF. Science 240: 1529-31, 1988

    Google Scholar 

  109. Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M, Pierce J, Aaronson S: Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science 243: 800-4, 1989

    Google Scholar 

  110. Hammacher A, Mellstrom K, Heldin CH, Westermark B: Isoform-specific induction of actin reorganization by platelet-derived growth factor suggests that the functionally active receptor is a dimer. EMBO J 8: 2489-95, 1989

    Google Scholar 

  111. Kanakaraj P, Raj S, Khan SA, Bishayee S: Ligand-induced interaction between alpha-and beta-type platelet derived growth factor (PDGF) receptors: role of receptor heterodimers in kinase activation. Biochemistry 30: 1761-7, 1991

    Google Scholar 

  112. Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray M, Bowen-Pope DF: Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem 264: 8771-8, 1989

    Google Scholar 

  113. Chiu IM, Reddy EP, Givol D, Robbins KC, Tronic SR, Aaronson SA: Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derivied growth factor. Cell 37: 123-9, 1984

    Google Scholar 

  114. Betsholtz CH, Johnsson A, Heldin C, Westermark B: Efficient reversion of simian sarcoma virus-transformation and inhibition of growth factor induced mitogenesis by suramin. Proc Natl Acad Sci USA 83: 6440-4, 1986

    Google Scholar 

  115. Rao CD, Igarashi H, Chin IM, Robbins KC, Aaronson SA: Structure and sequence of the human c-sis platelet-derived growth factor 2 (sis/PDGF2) transcriptional unit. Proc Natl Acad Sci USA 83: 2392-6, 1986

    Google Scholar 

  116. Beckmann MP, Betsholtz C, Heldin CH, Westermark B, DiMarco E, DiFiore PP, Robbins KC, Aaronson SA: Comparison of the biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science 241: 1346-9, 1988

    Google Scholar 

  117. La Rochelle WJ, Giese N, May-Siroff M, Robbins KC, Aaronson SA: Molecular localisation of the transforming and secretory properties of PDGF-A and PDGF-B. Science 248: 1541-4, 1990

    Google Scholar 

  118. Hermanson M, Funa K, Hartman M, Claesson-Weish L, Heldin CH, Westermark B, Nister M: Platelet-derived growth factor and its receptors in human glioma tissue: Expression of mRNA and protein suggests the presence of autocrine and paracrine loops. Cancer Res 52: 3212-9, 1992

    Google Scholar 

  119. Hermansson M, Nister M, Betsholtz C, Heldin CH, Westermark B, Funa K: Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet-derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation. Proc Natl Acad Sci 85: 7748-52, 1988

    Google Scholar 

  120. Nister M, Liebermann TA, Betsholtz C, Petterson M, Claesson-Welsh L, Heldin CH, Schlessinger J, Westermark B: Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-alpha and their receptors in human malignant glioma cell lines. Cancer Res 48: 3910-18, 1988

    Google Scholar 

  121. Mercola M, Deininger PL, Shamah SM, Porter J, Wang CY, Stiles CD: Dominant-negative mutants of a platelet-derived growth factor gene. Genes Dev 4: 2333-41. 1990

    Google Scholar 

  122. Guha A: Platelet derived growth factor: A general review with emphasis on astrocytomas. Pediatr Neurosurg 17: 14-20, 1991-1992

    Google Scholar 

  123. Shamah SM, Stiles CD, Guha A: Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. Mol Cell Biol 13: 7203-12, 1993

    Google Scholar 

  124. Guha A, Dashner K, Black, PM, Wagner JA, Stiles CD: Expression of PDGR and PDGF receptors in human astrocytoma operative specimens supports the existence of an autocrine loop. Int J Cancer 60: 168-73, 1995

    Google Scholar 

  125. Di Rocco F, Carroll RS, Zhang J, Black PM: Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery 42: 341-6, 1998

    Google Scholar 

  126. Plate KH, Breier G, Farrell C, Risau W: Platelet-derived growth factor-B is induced during tumor development and upregulated during tumor progression in endothelial cell in human gliomas. Lab Invest 67: 529-34, 1992

    Google Scholar 

  127. Risau W, Drexler H, Mironov V, Smits A, Siegbahn A, Funa K, Heldin C: Platelet-derived growth factor is angiogenic in vivo. Growth Factors 7: 261-6, 1992

    Google Scholar 

  128. Westermark B, Siegbahn A, Heldin CH, Claesson-Welsh L: B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein tyrosine kinase. Proc Natl Acad Sci USA 87: 128-32, 1990

    Google Scholar 

  129. Wang D, Su Huang HJ, Kazlauskas A, Cavanee WK: Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. Cancer Res 59: 1464-72, 1999

    Google Scholar 

  130. Maxwell M, Galanopoulos T, Hedley-Whyte ET, Black PM, Antoniades HN: Human meningiomas coexpress platelet-derived growth factor (PDGF) and PDGF-receptor genes and their protein products. Int J Cancer 46: 16-21, 1990

    Google Scholar 

  131. Mapstone T, McMichael M, Goldthwait D: Expression of platelet-derived growth factors, transforming growth factors, and the ras gene is a variety of primary human brain tumors. Neurosurgery 28: 216-22, 1991

    Google Scholar 

  132. Carpenter G, Cohen S: Epidermal growth factor. Annu Rev Biochem 48: 193-216, 1979

    Google Scholar 

  133. Todaro GH, Fryling C, Delakco JE: Transforming growth factors produced by certain human tumor cells: polypeptides that interact with human EGF-receptors. Proc Natl Acad Sci USA 77: 5258-62, 1980

    Google Scholar 

  134. Alroy I, Yarden Y: The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett 410: 83-6, 1997

    Google Scholar 

  135. Feldkamp MM, Lau N, Guha A: Signal transduction pathways and their relevance in human astrocytomas. J Neuro-Oncol 35: 223-48, 1997

    Google Scholar 

  136. Carpenter G: Epidermal growth factor: biology and receptor metabolism. J Cell Sci 3: 1-9, 1985

    Google Scholar 

  137. Derynck R, Roberts AB, Winkler ME, Chen EY, Goeddel DV: Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell 38: 287-97, 1984

    Google Scholar 

  138. Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klabsbrun M: Aheparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science 251: 936-9, 1991

    Google Scholar 

  139. Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M: The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. Mol Cell Biol 10: 1969-81, 1990

    Google Scholar 

  140. Komurasaki T, Toyoda H, Uchida D, Morimoto S: Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene 4: 2841-8, 1997

    Google Scholar 

  141. Zabel BU, Eddy RL, Lalley PA, Scott J, Bell GI, Shows TB: Chromosomal locations of the human and mouse genes for precursors of epidermal growth factor and the beta subunit of nerve growth factor. Proc Natl Acad Sci USA 82: 469-73, 1985

    Google Scholar 

  142. Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P: The epidermal growth factor. Cell Biol Int 19: 413-30, 1995

    Google Scholar 

  143. Tricoli JV, Nakai H, Byers MG, Rall LB, Bell GI, Shows TB: The gene for human transforming growth factor alpha is on the short arm of chromosome 2. Cytogenet Cell Genet 42: 94-8, 1986

    Google Scholar 

  144. DeLarco J, Todaro GJ: Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71. Cell 8: 365-71, 1976

    Google Scholar 

  145. Von Bossanyi P, Sallaba J, Dietzmann K, Warich-Kirches M, Kirches E: Correlation of TGF-alpha and EGF Receptor with proliferative activity in human astrocytic gliomas. Pathol Res Pract 194: 141-8, 1998

    Google Scholar 

  146. Kumar V, Bustin SA, McKay IA: Transforming growth factor alpha. Cell Biol Int 19: 373-88, 1995

    Google Scholar 

  147. Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD: Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307: 521-7, 1984

    Google Scholar 

  148. Kondo I, Shimizu N: Mapping of the human gene for the epidermal growth receptor (EGFR) gene on the p13-q22 region on chromosome 7. Cytogenet Cell Genet 35: 9-14, 1983

    Google Scholar 

  149. Heldin CH: Dimerization of cell surface receptors in signal transduction. Cell 80: 213-23, 1995

    Google Scholar 

  150. Soltoff SP, Carraway III KL, Prigent SA, Gullick WG, Cantley LC: ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor. Mol Cell Biol 14: 3550-8, 1994

    Google Scholar 

  151. Murali R, Brennan PJ, Kieber-Emmons T, Greene MI: Structural analysis of p185(cneu) and epidermal growth factor receptor tyrosine kinases: Oligomerization of kinase domains. Proc Natl Acad Sci USA 93: 6252-7, 1996

    Google Scholar 

  152. Earp HS, Dawson TL, Li X, Yu H: Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat 35: 115-32, 1995

    Google Scholar 

  153. Lemmon MA, Bu Z, Ladbury JE, Zhou M, Pinchasi D, Lax I. Engelman DM, Schlessinger J: Two EGF molecules contribute additively to stabilization of the EGFR dimer. EMBO 16: 281-94, 1997

    Google Scholar 

  154. Guha A: Ras activation in astrocytomas and neurofibromas. Can J Neurol Sci 25: 267-81, 1998

    Google Scholar 

  155. Steck PA, Lee P, Hung MC, Yung WK: Expression of an altered epidermal growth factor receptor by human glioblastoma cells. Cancer Res 48: 5433-9, 1988

    Google Scholar 

  156. Ekstrand AJ, Longo N, Hamid ML, Olson JJ, Liu L, Collins VP, James CD: Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. Oncogene 9: 2315-20, 1994

    Google Scholar 

  157. Nishikawa R, Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ: A mutant epidermal growth factor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91: 7727-31, 1994

    Google Scholar 

  158. Goike HM, Asplund AC, Pettersson EH, Liu L, Sanodou D, Collins VP: Acquired rearrangement of an amplified epidermal growth factor receptor (EGFR) in a human glioblastoma xenograft. J Neuropathol Exp Neurol 58: 697-701, 1999

    Google Scholar 

  159. Ekstrand AJ, Sugawa N, James CD, Collins VP: Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N-and/or C-terminal tails. Proc Natl Acad Sci USA 89: 4309-13, 1992

    Google Scholar 

  160. Torp SH, Helseth E, Dalen A, Unsgaard G: Epidermal growth factor receptor expression in human gliomas. Cancer Immunol Immunother 33: 61-4, 1991

    Google Scholar 

  161. Libermann TA, Razon N, Bantal AD, Yarden Y, Schlessinger J, Soreq H: Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 44: 753-60, 1984

    Google Scholar 

  162. Arita N, Hayakawa T, Izumoto S, Taki T, Ohnishi T, Yamamoto H, Bitoh S, Mogami H: Epidermal growth factor in human glioma. J Neurosurg 70: 916-19, 1989

    Google Scholar 

  163. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield M, Ullrich A, Schlessinger J: Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human tumors of glial origin. Nature 313: 144-7, 1985

    Google Scholar 

  164. Collins VP: Gene amplification in human gliomas. Glia 15: 289-96, 1995

    Google Scholar 

  165. Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B: Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84: 6899-903, 1987

    Google Scholar 

  166. Ekstrand AJ, James CD, Cavenee WK, Seliger B, Petterson RF, Collins VP: Genes for epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 51: 2164-72, 1991

    Google Scholar 

  167. Hurtt MR, Moosy J, Donovan-Peluso M, Locker J: Amplification of epidermal growth factor in gliomas: histopathology and prognosis. J Neuropathol Exp Neurol 51: 84-90, 1992

    Google Scholar 

  168. Newcomb EW, Cohen H, Lee SR, Bhalla SK, Bloom J, Hayes RL, Miller DC: Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol 8: 655-67, 1998

    Google Scholar 

  169. Bello L: Urinary epidermal growth factor (EGF) levels and epidermal growth factor receptor (EGF-R) expression in human cerebral tumors. J Neurosurg Sci 40: 167-82, 1996

    Google Scholar 

  170. Haapasalo H, Hyytinen E, Sallinen P, Helm H, Kallioniemi OP, Isola J: c-erbB-2 in astrocytomas: infrequent overexpression by immunohistochemistry and absence of gene amplification by fluorescence in situ hybridization. Br J Cancer 73: 620-3, 1996

    Google Scholar 

  171. Nickell KA, Halper J, Moses HL: Transforming growth factors in solid human malignant neoplasms. Cancer Res 43: 1966-71, 1983

    Google Scholar 

  172. Tang P, Steck PA, Yung WKA: The autocrine loop of TGF-a/EGFR and brain tumors. J Neuro-Oncol 35: 303-14, 1997

    Google Scholar 

  173. Maruno M, Kovach JS, Kelly PJ, Yanagihara T: Transforming growth factor-a, epidermal growth factor receptor, and proliferating potential in benign and malignant gliomas. J Neurosurg 75: 97-102, 1991

    Google Scholar 

  174. Schlegel U, Moots PL, Rosenblum MK, Thaler HT, Furneaux HM: Expression of transforming growth factor alpha in human gliomas. Oncogene 5: 1839-42, 1990

    Google Scholar 

  175. Yung WK, Zhang X, Steck PA, Hung MC: Differential amplification of the TGF-alpha gene in human gliomas. Cancer Comm 2: 201-5, 1990

    Google Scholar 

  176. Diedrich U, Lucius J, Baron E, Behnke J, Pabst B, Zoll B: Distribution of epidermal growth factor receptor gene amplification in brain tumours and correlation to prognosis. J Neurol 242: 683-8, 1995

    Google Scholar 

  177. Tang P, Jasser SA, Sung JC, Shi Y, Steck PA, Yung WKA: Transforming growth factor-alpha antisense vectors can inhibit glioma cell growth. J Neuro-Oncol 43: 127-35, 1999

    Google Scholar 

  178. U HS, Expiritu OD, Kelley PY, Klauber MR, Hatton JD: The role of the epidermal growth factor receptor in human gliomas: I. The control of cell growth. J Neurosurg 82: 841-6, 1995

    Google Scholar 

  179. Schreiber AB, Windler ME, Derynck R: Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science 232: 1250-3, 1986

    Google Scholar 

  180. Okamura K, Morimoto A, Hamanaka R, Ono M, Kohno K, Uchida Y, Kuwano M: A model system for tumor angiogenesis: involvement of transforming growth factor-alpha in tube formation of human microvascular endothelial cells induced by esophageal cancer cells. Biochem Biophys Res Commun 186: 1471-9, 1992

    Google Scholar 

  181. Goldman CK, Kim J, Wong WL, King V, Brock T, Gillespie GY: Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell 4: 121-33, 1993

    Google Scholar 

  182. Valter MM, Wiestler OD, Pietsche T: Differential control of VEGF synthesis and secretion in human glioma cells by IL-1 and EGF. Int J Devl NeuroScience 17: 565-77, 1999

    Google Scholar 

  183. Feldkamp MM, Lau N, Rak J, Kerbel RS, Guha A: Normoxic and hypoxic regulation of vascular endothelial growth factor (VEGF) by astrocytoma cells is mediated by ras. Int J Cancer 81: 118-24, 1999

    Google Scholar 

  184. Dorwald NL, Hawkins RA, Whittle IR: Epidermal growth factor receptor activity and clinical outcome in glioblastoma multiforme. Br J Neurosurg 7: 197-200, 1993

    Google Scholar 

  185. Attisano L, Wrana JL, Lopez-Casillas F, Massague J: TGF-beta receptors and actions. Biochim Biophys Acta 1222: 71-80, 1994

    Google Scholar 

  186. Massague J: The transforming growth factor-beta family. Annu Rev Cell Biol 6: 597-641, 1990

    Google Scholar 

  187. Engel ME, Datta PK, Moses HL: Signal transduction by transforming growth factor-beta: a cooperative paradigm with extensive negative regulation. J Cell Biochem (Suppl 30-31): 111-22, 1998

  188. Fujii D, Brissenden JE, Derynck R, Francke U: Transforming growth factor beta gene maps to human chromosome 19 long arm and to mouse chromosome 7. Somat Cell Mol Genet 12: 281-8, 1986

    Google Scholar 

  189. Barton DE, Foellmer BE, Du J, Tamm J, Derynck R, Francke U: Chromosomal mapping of genes for transforming growth factors beta 2 and beta 3 in man and mouse: dispersion of TGF-beta gene family. Oncogene Res 3: 323-31, 1988

    Google Scholar 

  190. ten Dijke P, Geurts van Kessel AH, Foulkes JG, Le Beau MM: Transforming growth factor type beta 3 maps to human chromosome 14, region q23-q24. Oncogene 3: 721-4, 1988

    Google Scholar 

  191. Massague J, Cheifetz S, Laiho M, Ralph DA, Weis FMB, Zentella A: Transforming Growth Factor-beta. In: Cancer Surveys Vol.12: Tumour Suppressor Genes, the Cell Cycle, and Cancer. Imperial Cancer Research Fund, 1992

  192. Cheifetz S, Like B, Massague J: Cellular distribution of type I and type II receptors for transforming growth factor-beta. J Biol Chem 261: 9972-78, 1986

    Google Scholar 

  193. Massague J, Andres J, Attisano L, Cheifetz S, Lopez-Casillas F, Ohtsuki M, Wrana JL: TGF-beta receptors. Mol Reprod Dev 32: 99-104, 1992

    Google Scholar 

  194. Morello JP, Plamondon J, Meyrick B, Hoover R, O'Connor-McCourt MD: Transforming growth factor-beta receptor expression on endothelial cells: heterogeneity of type III receptor expression. J Cell Physiol 165: 201-11, 1995

    Google Scholar 

  195. Gougos A, Letarte M: Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265: 8361-4, 1990

    Google Scholar 

  196. Pasche B, Luo Y, Rao PH, Nimer SD, Dmitrovsky E, Caron P, Luzzatto L, Offit K, Cordon-Cardo C, Renault B, Satagopan JM, Murty VV, Massague J: Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract. Cancer Res 58: 2727-32, 1998

    Google Scholar 

  197. Mathew S, Murty VV, Cheifetz S, George D, Massague J, Chaganti RS: Transforming growth factor receptor gene TGFbetaR2 maps to human chromosome band 3p22. Genomics 20: 114-5, 1994

    Google Scholar 

  198. Johnson DW, Qumsiyeh M, Benkhalifa M, Marchuk DA: Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFbetaR1 and TGFbetaR3) to 9q33-q34 and 1p32-p33, respectively. Genomics 28: 356-7, 1995

    Google Scholar 

  199. Fernandez-Ruiz E, St-Jacques S, Bellon T, Letarte M, Bernabeu C: Assignment of the human endoglin gene (END) to 9q34-〉qter. Cytogenet Cell Genet 64: 204-7, 1993

    Google Scholar 

  200. Samuels V, Barrett JM, Bockman S, Pantazis, Allen MG Jr: Immunocytochemical study of transforming growth factor expression in benign and malignant gliomas. Am J Pathol 134: 895-902, 1989

    Google Scholar 

  201. Horst HA, Kelly PJ, Scheithauer BW, Kovach JS: Immunohistological localization of transforming growth factor-beta in human astrocytomas. Hum Pathol 23: 1284-8, 1992

    Google Scholar 

  202. Yamada N, Kato M, Yamashita H, Nister N, Miyazono K, Heldin CH, Funa K: Enhanced expression of transforming growth factor-beta and its type-I and type-Il receptors in human glioblastoma. mt J Cancer 62: 386-92, 1995

    Google Scholar 

  203. Jennings M, Maciunas R, Carver R, Bascom C, Juneau P, Misulus K, Moses H: TGFbeta1 and TGFbeta2 are potential growth regulators for low-grade and malignant gliomas in vitro evidence in support of an autocrine hypothesis. Int J Cancer 49: 129-39, 1991

    Google Scholar 

  204. Stiles JD, Ostrow PT, Balos LL, Greenberg SJ, Plunkett R, Grand W, Heffner RR Jr: Correlation of endothelin-1 and transforming growth factor beta1 with malignancy and vascularity in human gliomas. J Neuropathol Exp Neurol 56: 435-9, 1997

    Google Scholar 

  205. Segarini PR, Rosen DM, Seydin SM: Binding of transforming growth factor-beta to cell surface proteins varies with cell type. Molec Endocr 3: 261-72, 1989

    Google Scholar 

  206. Hirai R, Kaji K: Transforming growth factor beta1-specific binding proteins on human vascular endothelial cells. Exp Cell Res 201: 119-25, 1992

    Google Scholar 

  207. Majewski C, Blisard K, Ballard E, Blair P, Qadir K, Bokhari S, Raza A, Lampkin B: Prognostic significance of immunohistochemical detection of transforming growth factor beta (TGF-beta) in central nervous system (CNS) neoplasia. (Abstract) Growth Control in Central Nervous System International workshop. Boston Massachusetts April 30-May, 1993

  208. Merzak A, McCrea S, Koocheckpoor S, Pilkington G: Control of human glioma cell growth, migration and invasion in vitro by transforming growth factor beta1. Br J Cancer 70: 199-203, 1994

    Google Scholar 

  209. Matsushita M, Matsuzaki K, Date M, Watanabe T, Shibano K, Nakagawa T, Yanagitani S, Amoh Y, Takemoto H, Ogata N, Yamamoto C, Kubota Y, Seki T, Inokuchi H, Nishizawa M, Takada H, Sawamura T, Okamura A, Inoue K: Down-regulation of TGF-beta receptors in human colorectal cancer: implications for cancer development. Br J Cancer 80: 194-205, 1999

    Google Scholar 

  210. Jennings MT, Hart CE, Commers PA, Whitlock JA, Martincic D, Maciunas RJ, Moots PL, Shehab TM: Transforming growth factor beta as a potential tumor progression factor among hyperdiploid glioblastoma cultures: evidence for the role of platelet-derived growth factor. J Neuro-Oncol 31: 233-54, 1997

    Google Scholar 

  211. Press RD, Misra A, Gillaspy G, Samols D, Goldthwait DA: Control of the expression of c-sis mRNA in human glioblastoma cells by phorbol ester and transforming growth factor beta 1. Cancer Res 49: 2914-20, 1989

    Google Scholar 

  212. Fajardo LF, Prionas SD, Kwan HH, Kowalski J, Allison AC: Transforming Growth Factor beta 1 induces angiogenesis in vivo with a threshold pattern. Lab Invest 74: 600-8, 1996

    Google Scholar 

  213. Baird A, Durkin T: Inhibition of endothelial cell proliferation by type beta-transforming growth factor: interactions with acidic and basic fibroblast growth factors. Biochem Biophys Res Commun 138: 476-82, 1986

    Google Scholar 

  214. Frater-Schroder M, Muller G, Birchmeier W, Bohlen P: Transforming growth factor-beta inhibits endothelial cell proliferation. Biochem Biophys Res Commun 137: 295-302, 1986

    Google Scholar 

  215. Heimark RL, Twardzik DR, Schwartz SM: Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 233: 1078-1080, 1986

    Google Scholar 

  216. RayChaudhury A, D'Amore PA: Endothelial cell regulation by transforming growth factor-beta. J Cell Biochem 47: 224-9, 1991

    Google Scholar 

  217. Pepper MS: Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 8: 21-43, 1997

    Google Scholar 

  218. Pepper MS, Vassalli J-D, Orci L, Montesano R: Biphasic effect of transforming growth factor-beta 1 on in vitro angiogenesis. Exp Cell Res 204: 356-63, 1993

    Google Scholar 

  219. Starksen NF, Harsh GR, Gibbs VC, Williams LT: Regulated expression of the platelet-derived growth factor A chain gene in microvascular endothelial cells. J Biol Chem 262: 14381-4, 1987

    Google Scholar 

  220. Kavanaugh WM, Harsh GR, Starksen NF, Rocco CM, Williams LT: Transcriptional regulation of the A and B chains of platelet-derived growth factor in microvascular endothelial cells. J Biol Chem 263: 8470-2, 1988

    Google Scholar 

  221. Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R: TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 63: 515-24, 1990

    Google Scholar 

  222. Helseth E, Unsgaard G, Dalen A, Vik R: The effects of type beta transforming growth factor on proliferation and epidermal growth factor receptor expression in a human glioblastoma line. J Neuro-Oncol 6: 269-76, 1988

    Google Scholar 

  223. Koochekpour S, Merzak A, Pilkington GJ: Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. Cancer Lett 102: 209-15, 1996

    Google Scholar 

  224. Saadeh PB, Mehrara BJ, Steinbrech DS, Dudziak ME, Greenwald JA, Luchs JS, Spector JA, Ueno H, Gittes GK, Longaker MT: Transforming growth factor-beta1 modulates the expression of vascular endothelial growth factor by osteoblasts. Am J Physiol 277: C628-37, 1999

    Google Scholar 

  225. Donovan D, Harmey JH, Toomey D, Osborne DH, Redmond HP, Bouchier-Hayes DJ: TGF beta-1 regulation of VEGF production by breast cancer cells. Ann Surg Oncol 4: 621-7, 1997

    Google Scholar 

  226. Bodey B, Bodey B Jr, Siegel SE, Kaiser HE: Upregulation of endoglin (CD105) expression during childhood brain tumor-related angiogenesis: Anti-angiogenic therapy. Anticancer Res 18: 1485-1500, 1998

    Google Scholar 

  227. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP: Defective angiogenesis in mice lacking endoglin. Science 284: 1534-7, 1999

    Google Scholar 

  228. Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M: Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 267: 19027-30, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dunn, I.F., Heese, O. & Black, P.M. Growth Factors in Glioma Angiogenesis: FGFs, PDGF, EGF, and TGFs. J Neurooncol 50, 121–137 (2000). https://doi.org/10.1023/A:1006436624862

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006436624862

Navigation