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Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants

  • Tumor Angiogenesis
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References

  1. Folkman J: What is the evidence that tumors are angiogenesis dependent. J Nat Cancer Inst 82: 4–7, 1990

    Google Scholar 

  2. Folkman J: Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med 1: 27–31, 1995

    Google Scholar 

  3. Rak JW, Stcroix BD, Kerbel RS: Consequences of angiogenesis for tumor progression, metastasis, and cancer therapy. Anti-Cancer Drug 6: 3–18, 1995

    Google Scholar 

  4. Ferrara N, Henzel WJ: Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161: 851–858, 1989

    Google Scholar 

  5. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246: 1306–1309, 1989

    Google Scholar 

  6. Tischer E, Gospodarowicz D, Mitchell R, Silva M, Schilling J, Lau K, Crisp T, Fiddes JC, Abraham JA: Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family. Biochem Biophys Res Commun 165: 1198–1206, 1989

    Google Scholar 

  7. Gospodarowicz D, Abraham JA, Schilling J: Isolation and characterization of a vascular endothelial cell mitogen produced by pituitary-derived folliculo stellate cells. Proc Natl Acad Sci USA 86: 7311–7315, 1989

    Google Scholar 

  8. Connolly DT, Olander JV, Heuvelman D, Nelson R, Monsell R, Siegel N, Haymore BL, Leimgruber R, Feder J: Human vascular permeability factor. Isolation from U937 cells. J Biol Chem 264: 20017–20024, 1989

    Google Scholar 

  9. 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: 1309–1312, 1989

    Google Scholar 

  10. Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG: Isolation of a human placental cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 88: 9267–9271, 1991

    Google Scholar 

  11. Guidi AJ, Abujawdeh G, Berse B, Jackman RW, Tognazzi K, Dvorak HF, Brown LF: Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Nat Cancer Inst 87: 1237–1245, 1995

    Google Scholar 

  12. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR: Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143: 1255–1262, 1993

    Google Scholar 

  13. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Senger DR, Dvorak HF: Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53: 4727–4735, 1993

    Google Scholar 

  14. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N: Inhibition of vascular endothelial growth factor induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841–844, 1993

    Google Scholar 

  15. Ferrara N, Winer J, Burton T, Rowland A, Siegel M, Phillips HS, Terrell T, Keller GA, Levinson AD: Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells. J Clin Invest 91: 160–170, 1993

    Google Scholar 

  16. Neufeld G, Tessler S, Gitay-Goren H, Cohen T, Levi BZ: Vascular endothelial growth factor and its receptors. Prog Growth Factor Res 5: 89–97: 1994

    Google Scholar 

  17. Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes JC, Abraham JA: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266: 11947–11954, 1991

    Google Scholar 

  18. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW: The vascular endothelial growth factor family-identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5: 1806–1814, 1991

    Google Scholar 

  19. Charnock-Jones SD, Sharkey AM, Rajput-Williams J, Burch D, Schofield JP, Fountain SA, Boocock C, Smith SK: Identification and localization of alternatively spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod 48: 1120–1128, 1993

    Google Scholar 

  20. Bacic M, Edwards NA, Merrill MJ: Differential expression of vascular endothelial growth factor (vascular permeability factor) forms in rat tissues-short communication. Growth Factors 12: 11–15, 1995

    Google Scholar 

  21. Cheung CY, Singh M, Ebaugh MJ, Brace RA: Vascular endothelial growth factor gene expression in ovine placenta and fetal membranes. Am J Obstet Gynecol 173: 753–759, 1995

    Google Scholar 

  22. Anthony FW, Wheeler T, Elcock CL, Pickett M, Thomas EJ: Identification of a specific pattern of vascular endothelial growth factor mRNA expression in human placenta and cultured placental fibroblasts. Placenta 15: 557–561, 1994

    Google Scholar 

  23. Plouet J, Schilling J, Gospodarowicz D: Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 8: 3801–3806, 1989

    Google Scholar 

  24. DiSalvo J, Bayne ML, Conn G, Kwok PW, Trivedi PG, Soderman DD, Palisi TM, Sullivan KA, Thomas KA: Purification and characterization of a naturally occurring vascular endothelial growth factor placenta growth factor heterodimer. J Biol Chem 270: 7717–7723, 1995

    Google Scholar 

  25. Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N: Dual regulation and vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 267: 26031–26037, 1992

    Google Scholar 

  26. Kondo S, Matsumoto T, Yokoyama Y, Ohmori I, Suzuki H: The shortest isoform of human vascular endothelial growth factor vascular permeability factor (VEGF/VPF121) produced by Saccharomyces cerevisiae promotes both angiogenesis and vascular permeability. Bba-Gen Subjects 1243: 195–202, 1995

    Google Scholar 

  27. Gengrinovitch S, Greenberg SM, Cohen T, Gitay-Goren H, Rockwell P, Maione TE, Levi B-Z, Neufeld G: Platelet factor-4 inhibits the mitogenic activity of VEGF-121 and VEGF-165 using several concurrent mechanisms. J Biol Chem 270: 15059–15065, 1995

    Google Scholar 

  28. Park JE, Keller GA, Ferrara N: Vascular endothelial growth factor (Vegf) isoforms-differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4: 1317–1326, 1993

    Google Scholar 

  29. Simon M, Grone HJ, Johren O, Kullmer J, Plate KH, Risau W, Fuchs E: Expressin of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Amer J Physiol-Renal Fl Elect 37: F240-F250, 1995

    Google Scholar 

  30. Morii K, Tanaka R, Washiyama K, Kumanishi T, Kuwano R: Expression of vascular endothelial growth factor in capillary hemangioblastoma. Biochem Biophys Res Commun 194: 749–755, 1993

    Google Scholar 

  31. Harrison-Woolrych ML, Sharkey AM, Charnock-Jones DS, Smith SK: Localization and quantification of vascular endothelial growth factor messenger ribonucleic acid in human myometrium and leiomyomata. J Clin Endocrinol Metab 80: 1853–1858, 1995

    Google Scholar 

  32. Cohen T, Gitay-Goren H, Sharon R, Shibuya M, Halaban R, Levi B-Z, Neufeld G: VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells. J Biol Chem 270: 11322–11326, 1995

    Google Scholar 

  33. Cohen T, Gitay-Goren H, Neufeld G, Levi B-Z: High levels of biologically active vascular endothelial growth factor (VEGF) are produced by the baculovirus expression system. Growth Factors 7: 131–138, 1992

    Google Scholar 

  34. Ferrara N, Houck K, Jakeman L, Leung DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 13: 18–32, 1992

    Google Scholar 

  35. Vaisman N, Gospodarowicz D, Neufeld G: Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 265: 19461–19466, 1990

    Google Scholar 

  36. Gitay-Goren H, Soker S, Vlodavsky I, Neufeld G: The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. J Biol Chem 267: 6093–6098, 1992

    Google Scholar 

  37. Gitay-Goren H, Cohen T, Tessler S, Soker S, Gengrinovitch S, Rockwell P, Klagsbrun M, Levi B-Z, Neufeld G: Selective binding of VEGF121 to one of the three VEGF receptors of vascular endothelial cells. J Biol Chem 271: 5519–5523, 1996

    Google Scholar 

  38. Soker S, Fidder H, Neufeld G, Klagsbrun M: Characterization of novel VEGF binding proteins associated with tumor cells that bind VEGF165 but not VEGF121. J Biol Chem 271: 5761–5767, 1996

    Google Scholar 

  39. Devries 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: 989–991, 1992

    Google Scholar 

  40. Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A: Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 367: 576–579, 1994

    Google Scholar 

  41. Seetharam L, Gotoh N, Maru Y, Neufeld G, Yamaguchi S, Shibuya M: A unique signal transduction from FLT tyrosine kinase, a receptor for vascular endothelial growth factor (VEGF). Oncogene 10: 135–147, 1995

    Google Scholar 

  42. Waltenberger J, Claessonwelsh L, Siegbahn A, Shibuya M, Heldin CH: Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 269: 26988–26995, 1994

    Google Scholar 

  43. Tessler S, Rockwell P, Cohen T, Levi B-Z, Hicklin D, Witte L, Lemischka IR, Neufeld G: Heparin modulates the interaction of VEGF165 with soluble and cell associated flk-1 receptors. J Biol Chem 269: 12456–12461, 1994

    Google Scholar 

  44. Schraufstatter IU, Halsey WA, Hyslop PA, Cochrane CG: In vitro models for the study of oxidant-induced injury of cells in inflammation. Methods Enzymol 163: 328–339, 1988

    Google Scholar 

  45. Heck DE, Laskin DL, Gardner CR, Laskin JD: Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. J Biol Chem 267: 21277–21280, 1992

    Google Scholar 

  46. Gospodarowicz D, Cheng J: Heparin protects basic and acidic FGF from inactivation. J Cell Physiol 128: 475–484, 1986

    Google Scholar 

  47. Volkin DB, Tsai PK, Dabora JM, Gress JO, Burke CJ, Linhardt RJ, Middaugh CR: Physical stabilization of acidic fibroblast growth factor by polyanions. Arch Biochem Biophys 300: 30–41, 1993

    Google Scholar 

  48. Vlodavsky I, Hua-Quan M, Danagher P, Ron D: Involvement of heparan-sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor. Cancer Metastasis Rev 1996, this issue

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Neufeld, G., Cohen, T., Gitay-Goren, H. et al. Similarities and differences between the vascular endothelial growth factor (VEGF) splice variants. Cancer Metast Rev 15, 153–158 (1996). https://doi.org/10.1007/BF00437467

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