Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Jul;17(7):4015–4023. doi: 10.1128/mcb.17.7.4015

Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.

S Yoshida 1, M Ono 1, T Shono 1, H Izumi 1, T Ishibashi 1, H Suzuki 1, M Kuwano 1
PMCID: PMC232254  PMID: 9199336

Abstract

Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms.

Full Text

The Full Text of this article is available as a PDF (856.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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. 1993 Jul;92(1):54–61. doi: 10.1172/JCI116599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asakuno K., Isono M., Wakabayashi Y., Mori T., Hori S., Kohno K., Kuwano M. The exogenous control of transfected c-fos gene expression and angiogenesis in cells implanted into the rat brain. Brain Res. 1995 Dec 8;702(1-2):23–31. doi: 10.1016/0006-8993(95)00880-8. [DOI] [PubMed] [Google Scholar]
  3. BenEzra D., Hemo I., Maftzir G. In vivo angiogenic activity of interleukins. Arch Ophthalmol. 1990 Apr;108(4):573–576. doi: 10.1001/archopht.1990.01070060121061. [DOI] [PubMed] [Google Scholar]
  4. Bussolino F., Camussi G., Baglioni C. Synthesis and release of platelet-activating factor by human vascular endothelial cells treated with tumor necrosis factor or interleukin 1 alpha. J Biol Chem. 1988 Aug 25;263(24):11856–11861. [PubMed] [Google Scholar]
  5. Clauss M., Gerlach M., Gerlach H., Brett J., Wang F., Familletti P. C., Pan Y. C., Olander J. V., Connolly D. T., Stern D. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med. 1990 Dec 1;172(6):1535–1545. doi: 10.1084/jem.172.6.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Defilippi P., Truffa G., Stefanuto G., Altruda F., Silengo L., Tarone G. Tumor necrosis factor alpha and interferon gamma modulate the expression of the vitronectin receptor (integrin beta 3) in human endothelial cells. J Biol Chem. 1991 Apr 25;266(12):7638–7645. [PubMed] [Google Scholar]
  7. Dionne C. A., Crumley G., Bellot F., Kaplow J. M., Searfoss G., Ruta M., Burgess W. H., Jaye M., Schlessinger J. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 1990 Sep;9(9):2685–2692. doi: 10.1002/j.1460-2075.1990.tb07454.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Duh E. J., Maury W. J., Folks T. M., Fauci A. S., Rabson A. B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5974–5978. doi: 10.1073/pnas.86.15.5974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elner V. M., Strieter R. M., Pavilack M. A., Elner S. G., Remick D. G., Danforth J. M., Kunkel S. L. Human corneal interleukin-8. IL-1 and TNF-induced gene expression and secretion. Am J Pathol. 1991 Nov;139(5):977–988. [PMC free article] [PubMed] [Google Scholar]
  10. Fajardo L. F., Kwan H. H., Kowalski J., Prionas S. D., Allison A. C. Dual role of tumor necrosis factor-alpha in angiogenesis. Am J Pathol. 1992 Mar;140(3):539–544. [PMC free article] [PubMed] [Google Scholar]
  11. Fidler I. J., Ellis L. M. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell. 1994 Oct 21;79(2):185–188. doi: 10.1016/0092-8674(94)90187-2. [DOI] [PubMed] [Google Scholar]
  12. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  13. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  14. Fràter-Schröder M., Risau W., Hallmann R., Gautschi P., Böhlen P. Tumor necrosis factor type alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5277–5281. doi: 10.1073/pnas.84.15.5277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gimbrone M. A., Jr, Gullino P. M. Neovascularization induced by intraocular xenografts of normal, preneoplastic, and neoplastic mouse mammary tissues. J Natl Cancer Inst. 1976 Feb;56(2):305–318. doi: 10.1093/jnci/56.2.305. [DOI] [PubMed] [Google Scholar]
  16. Hamanaka R., Kohno K., Seguchi T., Okamura K., Morimoto A., Ono M., Ogata J., Kuwano M. Induction of low density lipoprotein receptor and a transcription factor SP-1 by tumor necrosis factor in human microvascular endothelial cells. J Biol Chem. 1992 Jul 5;267(19):13160–13165. [PubMed] [Google Scholar]
  17. Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996 Aug 9;86(3):353–364. doi: 10.1016/s0092-8674(00)80108-7. [DOI] [PubMed] [Google Scholar]
  18. Hayashi T., Sekine T., Okamoto T. Identification of a new serine kinase that activates NF kappa B by direct phosphorylation. J Biol Chem. 1993 Dec 15;268(35):26790–26795. [PubMed] [Google Scholar]
  19. Hayashi T., Ueno Y., Okamoto T. Oxidoreductive regulation of nuclear factor kappa B. Involvement of a cellular reducing catalyst thioredoxin. J Biol Chem. 1993 May 25;268(15):11380–11388. [PubMed] [Google Scholar]
  20. Holmes W. E., Lee J., Kuang W. J., Rice G. C., Wood W. I. Structure and functional expression of a human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1278–1280. doi: 10.1126/science.1840701. [DOI] [PubMed] [Google Scholar]
  21. Ida N., Sakurai S., Hosoi K., Kunitomo T. A highly sensitive enzyme-linked immunosorbent assay for the measurement of interleukin-8 in biological fluids. J Immunol Methods. 1992 Nov 25;156(1):27–38. doi: 10.1016/0022-1759(92)90007-g. [DOI] [PubMed] [Google Scholar]
  22. Izumi H., Ono M., Ushiro S., Kohno K., Kung H. F., Kuwano M. Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human microvascular endothelial cells. Exp Cell Res. 1994 Oct;214(2):654–662. doi: 10.1006/excr.1994.1303. [DOI] [PubMed] [Google Scholar]
  23. Koch A. E., Polverini P. J., Kunkel S. L., Harlow L. A., DiPietro L. A., Elner V. M., Elner S. G., Strieter R. M. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 1992 Dec 11;258(5089):1798–1801. doi: 10.1126/science.1281554. [DOI] [PubMed] [Google Scholar]
  24. Kohno K., Hamanaka R., Abe T., Nomura Y., Morimoto A., Izumi H., Shimizu K., Ono M., Kuwano M. Morphological change and destabilization of beta-actin mRNA by tumor necrosis factor in human microvascular endothelial cells. Exp Cell Res. 1993 Oct;208(2):498–503. doi: 10.1006/excr.1993.1272. [DOI] [PubMed] [Google Scholar]
  25. Kondo S., Asano M., Suzuki H. Significance of vascular endothelial growth factor/vascular permeability factor for solid tumor growth, and its inhibition by the antibody. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1234–1241. doi: 10.1006/bbrc.1993.1955. [DOI] [PubMed] [Google Scholar]
  26. Krönke M., Schütze S., Scheurich P., Pfizenmaier K. TNF signal transduction and TNF-responsive genes. Immunol Ser. 1992;56:189–216. [PubMed] [Google Scholar]
  27. Leek R. D., Lewis C. E., Whitehouse R., Greenall M., Clarke J., Harris A. L. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996 Oct 15;56(20):4625–4629. [PubMed] [Google Scholar]
  28. Leibovich S. J., Polverini P. J., Shepard H. M., Wiseman D. M., Shively V., Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature. 1987 Oct 15;329(6140):630–632. doi: 10.1038/329630a0. [DOI] [PubMed] [Google Scholar]
  29. Lewis C. E., Leek R., Harris A., McGee J. O. Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol. 1995 May;57(5):747–751. doi: 10.1002/jlb.57.5.747. [DOI] [PubMed] [Google Scholar]
  30. Li Y., Mak G., Franza B. R., Jr In vitro study of functional involvement of Sp1, NF-kappa B/Rel, and AP1 in phorbol 12-myristate 13-acetate-mediated HIV-1 long terminal repeat activation. J Biol Chem. 1994 Dec 2;269(48):30616–30619. [PubMed] [Google Scholar]
  31. Libby P., Ordovas J. M., Auger K. R., Robbins A. H., Birinyi L. K., Dinarello C. A. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. Am J Pathol. 1986 Aug;124(2):179–185. [PMC free article] [PubMed] [Google Scholar]
  32. Lo Y. Y., Cruz T. F. Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J Biol Chem. 1995 May 19;270(20):11727–11730. doi: 10.1074/jbc.270.20.11727. [DOI] [PubMed] [Google Scholar]
  33. Lowenthal J. W., Ballard D. W., Böhnlein E., Greene W. C. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331–2335. doi: 10.1073/pnas.86.7.2331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Matsukura M., Shinozuka K., Zon G., Mitsuya H., Reitz M., Cohen J. S., Broder S. Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7706–7710. doi: 10.1073/pnas.84.21.7706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mawatari M., Kohno K., Mizoguchi H., Matsuda T., Asoh K., Van Damme J., Welgus H. G., Kuwano M. Effects of tumor necrosis factor and epidermal growth factor on cell morphology, cell surface receptors, and the production of tissue inhibitor of metalloproteinases and IL-6 in human microvascular endothelial cells. J Immunol. 1989 Sep 1;143(5):1619–1627. [PubMed] [Google Scholar]
  36. Mawatari M., Okamura K., Matsuda T., Hamanaka R., Mizoguchi H., Higashio K., Kohno K., Kuwano M. Tumor necrosis factor and epidermal growth factor modulate migration of human microvascular endothelial cells and production of tissue-type plasminogen activator and its inhibitor. Exp Cell Res. 1991 Feb;192(2):574–580. doi: 10.1016/0014-4827(91)90078-9. [DOI] [PubMed] [Google Scholar]
  37. Millauer B., Wizigmann-Voos S., Schnürch H., Martinez R., Møller N. P., Risau W., Ullrich A. High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell. 1993 Mar 26;72(6):835–846. doi: 10.1016/0092-8674(93)90573-9. [DOI] [PubMed] [Google Scholar]
  38. Montrucchio G., Lupia E., Battaglia E., Passerini G., Bussolino F., Emanuelli G., Camussi G. Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis. J Exp Med. 1994 Jul 1;180(1):377–382. doi: 10.1084/jem.180.1.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mukaida N., Shiroo M., Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366–1371. [PubMed] [Google Scholar]
  40. Murphy L. D., Herzog C. E., Rudick J. B., Fojo A. T., Bates S. E. Use of the polymerase chain reaction in the quantitation of mdr-1 gene expression. Biochemistry. 1990 Nov 13;29(45):10351–10356. doi: 10.1021/bi00497a009. [DOI] [PubMed] [Google Scholar]
  41. Murphy P. M., Tiffany H. L. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1280–1283. doi: 10.1126/science.1891716. [DOI] [PubMed] [Google Scholar]
  42. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Nomura M., Yamagishi S., Harada S., Hayashi Y., Yamashima T., Yamashita J., Yamamoto H. Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J Biol Chem. 1995 Nov 24;270(47):28316–28324. doi: 10.1074/jbc.270.47.28316. [DOI] [PubMed] [Google Scholar]
  44. 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. 1992 Aug 14;186(3):1471–1479. doi: 10.1016/s0006-291x(05)81572-4. [DOI] [PubMed] [Google Scholar]
  45. Okamura K., Sato Y., Matsuda T., Hamanaka R., Ono M., Kohno K., Kuwano M. Endogenous basic fibroblast growth factor-dependent induction of collagenase and interleukin-6 in tumor necrosis factor-treated human microvascular endothelial cells. J Biol Chem. 1991 Oct 15;266(29):19162–19165. [PubMed] [Google Scholar]
  46. Ono M., Okamura K., Nakayama Y., Tomita M., Sato Y., Komatsu Y., Kuwano M. Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha. Biochem Biophys Res Commun. 1992 Dec 15;189(2):601–609. doi: 10.1016/0006-291x(92)92243-q. [DOI] [PubMed] [Google Scholar]
  47. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pandey A., Shao H., Marks R. M., Polverini P. J., Dixit V. M. Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science. 1995 Apr 28;268(5210):567–569. doi: 10.1126/science.7536959. [DOI] [PubMed] [Google Scholar]
  49. Passaniti A., Taylor R. M., Pili R., Guo Y., Long P. V., Haney J. A., Pauly R. R., Grant D. S., Martin G. R. A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest. 1992 Oct;67(4):519–528. [PubMed] [Google Scholar]
  50. Patterson C., Perrella M. A., Hsieh C. M., Yoshizumi M., Lee M. E., Haber E. Cloning and functional analysis of the promoter for KDR/flk-1, a receptor for vascular endothelial growth factor. J Biol Chem. 1995 Sep 29;270(39):23111–23118. doi: 10.1074/jbc.270.39.23111. [DOI] [PubMed] [Google Scholar]
  51. Perkins N. D., Edwards N. L., Duckett C. S., Agranoff A. B., Schmid R. M., Nabel G. J. A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1 enhancer activation. EMBO J. 1993 Sep;12(9):3551–3558. doi: 10.1002/j.1460-2075.1993.tb06029.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  53. Pusztai L., Clover L. M., Cooper K., Starkey P. M., Lewis C. E., McGee J. O. Expression of tumour necrosis factor alpha and its receptors in carcinoma of the breast. Br J Cancer. 1994 Aug;70(2):289–292. doi: 10.1038/bjc.1994.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ramasamy S., Lipke D. W., McClain C. J., Hennig B. Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial cells. J Cell Physiol. 1995 Jan;162(1):119–126. doi: 10.1002/jcp.1041620114. [DOI] [PubMed] [Google Scholar]
  55. Ryuto M., Ono M., Izumi H., Yoshida S., Weich H. A., Kohno K., Kuwano M. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1. J Biol Chem. 1996 Nov 8;271(45):28220–28228. doi: 10.1074/jbc.271.45.28220. [DOI] [PubMed] [Google Scholar]
  56. Saffer J. D., Jackson S. P., Annarella M. B. Developmental expression of Sp1 in the mouse. Mol Cell Biol. 1991 Apr;11(4):2189–2199. doi: 10.1128/mcb.11.4.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Sato N., Fukuda K., Nariuchi H., Sagara N. Tumor necrosis factor inhibiting angiogenesis in vitro. J Natl Cancer Inst. 1987 Dec;79(6):1383–1391. [PubMed] [Google Scholar]
  58. Sato Y., Okamura K., Morimoto A., Hamanaka R., Hamaguchi K., Shimada T., Ono M., Kohno K., Sakata T., Kuwano M. Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro. Exp Cell Res. 1993 Feb;204(2):223–229. doi: 10.1006/excr.1993.1028. [DOI] [PubMed] [Google Scholar]
  59. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Schweigerer L., Malerstein B., Gospodarowicz D. Tumor necrosis factor inhibits the proliferation of cultured capillary endothelial cells. Biochem Biophys Res Commun. 1987 Mar 30;143(3):997–1004. doi: 10.1016/0006-291x(87)90350-0. [DOI] [PubMed] [Google Scholar]
  61. Schütze S., Potthoff K., Machleidt T., Berkovic D., Wiegmann K., Krönke M. TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown. Cell. 1992 Nov 27;71(5):765–776. doi: 10.1016/0092-8674(92)90553-o. [DOI] [PubMed] [Google Scholar]
  62. Shibata F., Baird A., Florkiewicz R. Z. Functional characterization of the human basic fibroblast growth factor gene promoter. Growth Factors. 1991;4(4):277–287. doi: 10.3109/08977199109043913. [DOI] [PubMed] [Google Scholar]
  63. Shono T., Ono M., Izumi H., Jimi S. I., Matsushima K., Okamoto T., Kohno K., Kuwano M. Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol. 1996 Aug;16(8):4231–4239. doi: 10.1128/mcb.16.8.4231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stoltz R. A., Abraham N. G., Laniado-Schwartzman M. The role of NF-kappaB in the angiogenic response of coronary microvessel endothelial cells. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2832–2837. doi: 10.1073/pnas.93.7.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Terman B. I., Dougher-Vermazen M., Carrion M. E., Dimitrov D., Armellino D. C., Gospodarowicz D., Böhlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1579–1586. doi: 10.1016/0006-291x(92)90483-2. [DOI] [PubMed] [Google Scholar]
  66. Tischer E., Mitchell R., Hartman T., Silva M., Gospodarowicz D., Fiddes J. C., Abraham J. A. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 1991 Jun 25;266(18):11947–11954. [PubMed] [Google Scholar]
  67. Wakabayashi Y., Shono T., Isono M., Hori S., Matsushima K., Ono M., Kuwano M. Dual pathways of tubular morphogenesis of vascular endothelial cells by human glioma cells: vascular endothelial growth factor/basic fibroblast growth factor and interleukin-8. Jpn J Cancer Res. 1995 Dec;86(12):1189–1197. doi: 10.1111/j.1349-7006.1995.tb03314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. de Vries C., Escobedo J. A., Ueno H., Houck K., Ferrara N., Williams L. T. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989–991. doi: 10.1126/science.1312256. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES