Abstract
The development of a vascular supply is a fundamental requirement for organ development and differentiation in multicellular organisms (Hamilton et al., 1962) and is also necessary for tissue repair and reproductive functions in the adult (Klagsbrun and D’Amore, 1991; Folkman and Shing, 1992). Angiogenesis is also implicated in the pathogenesis of a variety of disorders. These include: proliferative retinopathies, age-related macular degeneration, tumors, rheumatoid arthritis, and psoriasis (Klagsbrun and D’Amore, 1991; Folkman, 1991). In the case of proliferative retinopathies and age-related macular degeneration, the new blood vessels are directly responsible for many of the destructive events characteristic of these conditions (Garner, 1994). Conversely, in neoplasms the neovascularization provides nourishment to the growing tumor, thus allowing the tumor cells to express their critical growth advantage, and also permits the establishment of continuity with the vasculature of the host (Folkman, 1991). A strong correlation has been noted between density of microvessels in primary breast carcinoma sections, nodal metastases and survival (Weidner et al, 1991, 1992; Horak et al, 1992; Vartanian and Weidner, 1994). Similarly, a correlation has been reported between vascularity and invasive behavior in bladder (Chodak et al., 1980), prostate (Wakui et al., 1992; Bigler et al., 1993), non-small cell lung (Macchiarmi et al., 1992), and uterine cervix (Sillman et al., 1981) carcinomas and in cutaneous melanomas (Srivastava et al., 1988). Furthermore, recent studies have shown a statistically significant increase in microvessel count in severe uterine cervix dysplasia (CIN III) compared to low grade lesions (CIN I) (Smith-McCune et al., 1994).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adamis, A.P., Miller, J.W., Bernal, M.T., D’Amico, D., Folkman, J., Yeo, T.-K. and Yeo, K.-T. (1994) Increased vascular endothelial growth factor in the vitreous of eyes with proliferative diabetic retinopathy. Am. J. Ophthalmol. 118:445–450.
Adamis, A.P., Shima, D.T., Tolentino, M., Gragoudas, F, Ferrara, N., Folkman, J., D’Amore, P.A. and Miller, J.W. (1996) Inhibition of VEGF prevents iris neovascularization in a non-human primate. Arch. Ophthalmol, 114:66–71.
Aiello, L.P., Avery, R., Arrigg, R., Keyt, B., Jampel, H., Shah, S., Pasquale, L., Thieme, H., Iwamoto, M., Park, J.E., Nguyen, H., Aiello, L.M., Ferrara, N. and King, G.L. (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 331:1480–1487.
Aiello, L.P., Pierce, E.A., Foley, E.D., Takagi, H., Riddle, L., Chen, H., Ferrara, N., King, G.L. and Smith, L.E. (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc. Natl. Acad. Sci. USA 92:10457–10461.
Asahara, T., Bauters, C, Pastore, C, Bunting, S., Ferrara, N., Symes, J.F. and Isner, J.M. (1995) Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimai hyperplasia in balloon-injured rat carotid artery. Circulation 91:2802–2809.
Banai, S., Jaktlish, M.T., Shou, M, Lazarous, D.F., Scheinowitz, M., Biro, S., Epstein, S. and Unger, E. (1994 a) Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 89:2183–2189.
Banai, S., Shweiki, D., Pinson, A., Chandra, M., Lazarovici, G. and Keshet, E. (1994b) Upregulation of vascular endothelial growth factor expression induced by myocardial ischemia: implications for coronary angiogenesis. Cardiovasc. Res. 28:1176–1179.
Bauters, C, Asahara, T., Zheng, L.P., Takeshita, S., Bunting, S., Ferrara, N., Symes, J.F. and Isner, J.M. (1994) Physiologic assessment of augmented vascularity induced by VEGF in a rabbit ischemic hindlimb model. Am. J. Physiol. 267:H1263–H1271.
Bauters, C., Asahara, T., Zheng, L.P., Takeshita, S., Bunting, S., Ferrara, N., Symes, J.F. and Isner, J.M. (1995) Recovery of disturbed endothelium-dependent flow in collateral-perfused rabbit ischemic hindlimb following administration of VEGF. Circulation 91:2793–2801.
Berkman, R.A., Merrill, M.J., Reinhold, W.C., Monacci, W.T., Saxena, A., Clark, W.C., Robertson, J.T., Ali, LU. and Oldfield, E.H. (1993) Expression of the vascular permeability/vascular endothelial growth factor gene in central nervous system neoplasms. J. Clin. Invest. 91:153–159.
Bigler, S.A., Deering, R.E. and Brawer, M.K. (1993) Comparison of microscopic vascularity in benign and malignant prostatic tissue. Hum. Pathol. 24:220–226.
Borgström, P., Hillan, K.J., Sriramoa, S. and Ferrara, N. (1996) In vivo imaging of tumor vasculature by intravital microscopy: Inhibition of angiogenesis by anti-VEGF antibodies. Cancer Res. In press.
Breier, G., Albrecht, U., Sterrer, S. and Risau, W. (1992) Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 114:521–532.
Brown, L.F., Berse, B., Jackman, R.W., Tognazzi, K., Manseau, E.J., Dvorak, H.F., Senger, D.R. (1993 a) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am. J. Pathol. 143:1255–1262.
Brown, L.F., Berse, B., Jackman, R.W., Tognazzi, K., Manseau, E.J., Senger, D.R. and Dvorak, H.F. (1993 b) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res. 53:4727–4735.
Brown, L.F., Berse, B., Jackman, R.W., Guidi, A.J., Dvorak, H.F., Senger, D.R., Connolly, J.L. and Schnitt, S.J. (1995 a) Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum. Pathol. 26:86–91.
Brown, L.F, Harris, T.J., Yeo, K.T., Stahle-Backdahl, M., Jackman, R.W., Berse, B., Tognazzi, K., Dvorak, H.F. and Detmar, M. (1995b) Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis and herythema multiforme. J. Invest. Dermatol. 104:744–749.
Chodak, G.W., Haudenschild, C, Gittes, R.F and Folkman, J. (1980) Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder. Ann. Surg. 192:762–771.
Claffey, K.P., Wilkinson, W.O. and Spiegelman, B.M. (1992) Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways. J. Biol. Chem. 267:16317–16322.
Conn, G., Bayne, M., Soderman, L., Kwok, PW, Sullivan, K.A., Palisi, T.M., Hope, D.A. and Thomas, K.A. (1990) Amino acid and cDNA sequence of a vascular endothelial cell mitogen homologous to platelet-derived growth factor. Proc. Natl. Acad. Sci USA 87:2628–2632.
Connolly, D.T., Heuvelman, D.M., Nelson, R., Olander, J.V, Eppley, B.L., Delfino, J.J., Siegel, N.R., Leimgruber, R.M. and Feder, J. (1989 a) Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J. Clin. Invest. 84:1470–1478.
Connolly, D.T., Olander, J.V, Heuvelman, D., Nelson, R., Monsell, R., Siegel, N., Haymore, B.L., Leingruber, R. and Feder, J. (1989b) Human vascular permeability factor. Isolation from U937 cells. J. Biol. Chem. 254:20017–20024.
de Vries, C, Escobedo, J.A., Ueno, H., Houck, K.A., Ferrara, N. and Williams, L.T. (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989–991.
DiSalvo, J., Bayne, M.L., Conn, G., Kwok, PW, Trivedi, P.G., Soderman, D.D., Palisi, T.M., Sullivan, K.A. and Thomas, K.A. (1995) Purification and characterization of a naturally occurring vascular endothelial growth factor placenta growth factor heterodimer. J. Biol. Chem. 270:7717–7723.
Dvorak, H.F. (1986) Tumors: wound that do not heal. Similarity between tumor stroma generation and wound healing. N. Engl. J. Med. 315:1650–1658.
Dvorak, H.F., Harvey, VS., Estrella, P., Brown, L.F., McDonagh, J. and Dvorak, A.M. (1987) Fibrin containing gels induce angiogenesis: implications for tumor stroma generation and wound healing. Lab. Invest. 57:673–686.
Dvorak, H.F, Brown, L.F, Detmar, M. and Dvorak, A.M. (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular permeability and angiogenesis. Am. J. Pathol. 146:1029–1039.
Essed, CD., Brand, M.VD. and Becker, A.E. (1983) Transluminal coronary angioplasty and early restenosis. Br. Heart J. 49:393–402.
Fassbender, H.J. and Simling-Annefeld, M. (1983) The potential aggressiveness of synovial tissue in rheumatoid arthritis. J. Pathol. 139:399–406.
Fava, R.A., Olsen, N.J., Spencer-Green, G., Yeo, T.-K., Yeo, K.-T., Berse, B., Jackman, R.W., Senger, D.R., Dvorak, H.F. and Brown, L.F. (1994) Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid arthritis. J. Exp. Med. 180:340–346.
Ferrara, N. and Henzei, W.J. (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun. 161:851–859.
Ferrara, N., Houck, K., Jakeman, L. and Leung, D.W. (1992) Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr. Rev. 13:18–32.
Ferrara, N. (1993) Vascular endothelial growth factor. Trends Cardiovasc. Med. 3:244–250.
Ferrara, N. (1995) Vascular endothelial growth factor - The trigger for neovascularization in the eye. (Editorial) Lab. Invest. 72:615–618.
Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Hillan, K.J., Lu, L., O’Shea, S., Powell-Braxton, L. and Moore, M. (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442.
Folkman, J. (1991) What is the evidence that tumors are angiogenesis-dependent? J. Natl. Cancer Inst. 82:4–6.
Folkman, J. and Shing, Y Angiogenesis. J. Biol. Chem. 267:10931–10934.
Fong, G.-H., Rassant, J., Gertenstein, M. and Breitman, M. (1995) Role of Fit-1 receptor tyrosine kinase in regulation of assembly of vascular endothelium. Nature 376:6670.
Frank, S., Hubner, G., Breier, G., Longaker, M.T., Greenhalgh, D.G. and Werner, S. (1995) Regulation of VEGF expression in cultured keratinocytes. Implications for normal and impaired wound healing. J. Biol. Chem. 20:12607–12613.
Garner, A. (1994) Vascular diseases. In: A. Garner and G.K. Klintworth (eds): Pathobiology of ocular disease. A dynamic approach. 2nd Edition, Marcel Dekker, New York, pp 1625–1710.
Garrido, C, Saule, S. and Gospodarowicz, D. (1993) Transcriptional regulation of vascular endothelial growth factor gene expression in ovarian bovine granulosa cells. Growth Factors 8:109–117.
Goldberg, M.A. and Schneider, T.J. (1994) Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J. Biol. Chem. 269:4355–4361.
Graor, R.A. and Gray, B.H. (1991) Interventional treatment of peripheral vascular disease. In: J.R.Young, R.A. Graor, J.W. Olin and J.R. Bartholomew (eds): Peripheral Vascular Diseases, Mosby, St. Louis, pp 111–133.
Gross, J. and Nagai, Y. (1965) Specific degradation of the collagen molecule by tadpole collagenolytic enzyme. Proc. Natl. Acad. Sci. USA 54:1197–1204.
Hamilton, J. (1976) Hypothesis: In vitro evidence for the invasive and tumor-like properties of the rheumatoid pannus. J. Rheumatol. 10:845–851.
Hamilton, W.J., Boyd, J.D. and Mossman, H.W. (1962) Human Embryology, William & Wilkins, Baltimore.
Hannehan, A., deJuan, E., Lutti, G.A., Fox, G.M., Schiffer, S. and Hjelmeland, L.M. (1991) Altered distribution of basic fibroblast growth factor in diabetic retinopathy. Arch. Ophthalmol. 109:1005–1011.
Harada, K., Friedman, M., Lopez, J., Prasad, P.V, Hibberd, M., Pearlman, J.D., Sellke, F.W. and Simons, M. (1996) Vascular endothelial growth factor improves coronary flow and myocardial function in chronically ischemic porcine hearts. Am. J. Physiol. 270:1791–1802.
Hauser, S. and Weich, H.A. (1993) A heparin-binding form of placenta growth factor (P1GF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 9:259–268.
Horak, E.R., Leek, R., Klenk, N., Lejeune, S., Smith, K., Stuart, M., Greenall, M. and Harris, A.L. (1992) Quantitative angiogenesis assessed by anti-PECAM antibodies: correlation with node metastasis and survival in breast cancer. Lancet 340:1120–1124.
Houck, K.A., Ferrara, N., Winer, J., Cachianes, G., Li, B. and Leung, D.W. (1991) The vascular endothelial growth factor family: Identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol. Endocrinol 5:1806–1814.
Houck, K.A., Leung, D.W., Rowland, A.M., Winer, J. and Ferrara, N. (1992) Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J. Biol Chem. 267:26031–26037.
Jakeman, L.B., Winer, X, Bennett, G.L., Altar, C.A. and Ferrara, N. (1992) Binding sites for vascular endothelial growth factor rare localized on endothelial cells in adult rat tissues. J. Clin. Invest. 89:244–253.
Jakeman, L.B., Armanini, M., Phillips, H.S. and Ferrara, N. (1993) Developmental expression of binding sites and mRNA for vascular endothelial growth factor suggests a role or this protein in vasculogenesis and angiogenesis. Endocrinology 133:848–859.
Keck, P.J., Hauser, S.D., Krivi, G., Sanzo, K., Warren, T, Feder, J. and Connolly, D.T. (1989) Vascular permeability factor, an endothelial cell mitogen related to platelet derived growth factor. Science 246:1309–1312.
Keyt, B., Berleau, L., Nguyen, H., Chen, H., Heinsohn, H., Vandler, R. and Ferrara, N. (1996a) The Carboxy-Terminal Domain (111–165) of Vascular Endothelial Growth Factor is Critical for its Mitogenic Potency. J. Biol. Chem. 271:7788–7795.
Keyt, B., Nguyen, H., Berleau, L., Duarte, C, Park, J., Chen, H. and Ferrara, N. (1996b) Identification of VEGF Determinants for Binding KDR and FLT-1 Receptors. J. Biol Chem. 271(9): 5638–5646.
Kieser, A., Weich, H., Brandner, G., Marme, D. and Kolch, W. (1994) Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene 9:963–969.
Kim, K.J., Li, B., Houck, K., Winer, J. and Ferrara, N. (1992) The vascular endothelial growth factor proteins: Identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors 7:53–64.
Kim, K.J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H.S. and Ferrara, N. (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844.
Klagsbrun, M. and D’Amore, P.A. (1991) Regulators of angiogenesis. Ann. Rev. Physiol 53:217–239.
Koch, E., Harlow, I, Haines, G.K., Amento, E.P., Unemori, E.N., Wong, W.-L., Pope, R.M. and Ferrara, N. (1994) Vascular endothelial growth factor: a cytokine modulating endothelial function in rheumatoid arthritis. J. Immunol 152:4149–4155.
Ku, D.D., Zaleski, J.K., Liu, S. and Brock, T. (1993) Vascular endothelial growth factor induces EDRF-dependent relaxation of coronary arteries. Am. J. Physiol. 265, h 586–592.
Leung, D.W., Cachianes, G., Kuang, W.-J., Goeddel, D.V and Ferrara, N. (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309.
Levy, A.P., Levy, N.S., Wegner, S. and Goldberg, M.A. (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem. 270:13333–13340.
Li, J., Perrella, M.A., Tsai, J.C, Yet, S.F., Hsieh, CM., Yoshizumi, M., Patterson, C, Endego, W.O., Zhou, F. and Lee, M. (1995) Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells. J. Biol. Chem. 270:308–312.
Lyttle, D.J., Fraser, K.M., Flemings, S.B., Mercer, A.A. and Robinson, A.J. (1994) Homology of vascular endothelial growth factor are encoded by the poxvirus orf virus. J. Virol. 68:84–92.
Macchiarini, P., Fontanini, G., Hardin, M.J., Squartini, F. and Angeletti, C.A. (1992) Relation of neovascularization to metastasis of non-small cell lung carcinoma. Lancet 340:145–146.
Madan, A. and Curtin, PT. (1993) A 24-base pair sequence 3′ to the human erythropoietin contains a hypoxia-responsive transcriptional enhancer. Proc. Natl Acad. Sci. USA 90:3928–3932.
Maglione, D., Guerriero, V, Viglietto, G., Delli-Bovi, P. and Persico, M.G. (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc. Natl. Acad. Sci. USA 88:9267–9271.
Malecaze, F., Clemens, S., Simorer-Pinotel, V, Mathis, A., Chollet, P., Favard, P., Bayard, F. and Ploüet, J. (1994) Detection of vascular endothelial growth factor mRNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch. Ophthalmol. 112:1476–1482.
Mandriota, S., Montesano, R., Orci, L., Seghezzi, G., Vassalli, J.-D., Ferrara, N., Mignatti, P. and Pepper, M.S. (1995) Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J. Biol. Chem. 270:9709–9716.
Matthews, W., Jordan, C.T., Gavin, M., Jenkins, N.A., Copeland, N.G. and Lemischka, I.R. (1991) A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Proc. Natl. Acad. Sci. USA 88:9026–9030.
Meyer-Schwickerath, R., Pfeiffer, A., Blum, W.F., Freyberger, H., Klein, M., Losche, C, Rollman, R. and Schatz, H. (1993) Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3 increase in neovascular disease. J. Clin. Invest. 92:2620–2625.
Michaelson, I.C. (1948) The mode of development of the vascular system of the retina with some observations on its significance for certain retinal disorders. Trans. Ophthalmol. Soc. U.K. 68:137–180.
Mignatti, P., Tsuboi, R., Robbins, E. and Rifkin, D.B. (1989) In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-indue ed proteinases. J. Cell Biol. 108:671–682.
Millauer, B., Wizigmann-Voos, S., Schnurch, H., Martinez, R., Moller, N.P. Risau, W. and Ullrich, A. (1993) High affinity binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72:8358–846.
Millauer, B., Shawver, L.K., Plate, K.H., Risau, W. and Ullrich, A. (1994) Glioblastoma growth is inhibited in vivo by a negative dominant Flk-1 mutant. Nature 367:576–579.
Monacci, W., Merrill, M. and Oldfield, E. (1993) Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am. J. Physiol. 264:c995–cl002.
Mukhopadhyay, D., Tsilokas, L., Zhou, X.M., Foster, D., Brugge, J.S. and Sukhatme, Y.P. (1995) Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 375:577–581.
Mustonen, T. and Alitalo, K. (1995) Endothelial receptor tyrosine kinases involved in angiogenesis. J. Cell Biol. 129:895–898.
Nicosia, R.F, Nicosia, S.V and Smith, M. (1995) Vascular endothelial growth factor, platelet-derived growth factor and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am. J. Pathol. 145:1023–1029.
Oefner, C, D’Arcy, A., Winkler, F.K., Eggimann, B. and Hosang, M. (1992) Crystal Structure of human platelet-derived growth factor BB. EMBO J. 11:3921–3926.
Olk, R.J. and Lee, CM. (1993) Diabetic retinopathy: practical management. Lippincott Co. Philadelphia, PA.
Olson, T.A., Mohanraj, D., Carson, L.F. and Ramakrishnan, S. (1994) Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res. 54:276–280.
Park, J.E., Keller, G.-A. and Ferrara, N. (1993) The vascular endothelial growth factor (VEGF) isoforms: Differential deposition into the subepithelial extracellular matrix and bioactivity of ECM-bound VEGF. Mol. Biol. Cell 4:1317–1326.
Park, J.E., Chen, H., Winer, J., Houck, K. and Ferrara, N. (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J. Biol. Chem. 269:25646–25654.
Patz, A. (1980) Studies on retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 19:1133–1138.
Pe’er, J., Shweiki, D., Itin, A., Hemo, I., Gnessi, H. and Keshet, E. (1995) Hypoxia-induced expression of vascular endothelial growth factor (VEGF) by retinal cells in a common factor in neovascularization. Lab. Invest. 72:638–645.
Pekala, P., Marlow, M., Heuvelman, D. and Connolly, D. (1990) Regulation of hexose transport in aortic endothelial cells by vascular permeability factor and tumor necrosis factor-alpha, but not by insulin. J. Biol. Chem. 265:18051–18054.
Pepper, M.S. and Montesano, R. (1990) Proteolytic balance and capillary morphogenesis. Cell Diff. Dev. 32:319–331.
Pepper, M.S., Ferrara, N., Orci, L. and Montesano, R. (1991) Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor type 1 in microvascular endothelial cells. Biochem. Biophys. Res. Commun. 181:902–908.
Pepper, M.S., Ferrara, N., Orci, K. and Montesano, R. (1992) Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem. Biophys. Res. Commun. 189:824–831.
Pertovaara, L., Kaipainen, A., Mustonen, T., Orpana, A., Ferrara, N., Saksela, O. and Alitalo, K. (1994) Vascular endothelial growth factor is induced in response to transforming growth factor-ß in fibroblastic and epithelial cells. J. Biol. Chem. 269:6271–6274.
Peters, K.G., De Vries, C. and Williams, L.T. (1993) Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proc. Natl. Acad. Sci. USA 90:8915–8919.
Phillips, H.S., Hains, J., Leung, D.W. and Ferrara, N. (1990) Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology 127:965–968.
Phillips, G.D., Stone, A.M., Jones, B.D., Schultz, J.C, Whitehead, R.A. and Knighton, D.R. (1993) Vascular endothelial growth factor (rhVEGF 165) stimulates direct angiogenesis in the rabbit cornea. In Vivo 8:961–965.
Plate, K.H., Breier, G., Weich, H.A. and Risau, W. (1992) Vascular endothelial growth is a potential tumour angiogenesis factor in vivo. Nature 359:845–847.
Ploüet, J., Schilling, J. and Gospodarowicz, D. (1989) Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT20 cells. EMBO J. 8:3801–3807.
Quinn, T, Peters, K.G., de Vries, C, Ferrara, N. and Williams, L.T. (1993) Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc. Natl. Acad. Sci. USA 90:7533–7537.
Rak, J. Mitsuhashi, Y., Bayko, I., Filmus, J., Shirasawa, S., Sasazuki, T. and Kerbel, R.S. (1995) Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res. 55:4575–4580.
Ravindranath, N., Little-Ihrig, L., Phillips, H.S., Ferrara, N. and Zeleznick, A.J. (1992) Vascular endothelial growth factor mRNA expression in the primate ovary. Endocrinology 131: 254–260.
Rifkin, D.B., Moscatelli, D., Bizik, J., Quarto, N., Blei, F., Dennis, P., Flaumenhaft, R. and Mignatti, P. (1990) Growth factor control of extracellular proteolysis. Cell Differ. Dev. 32:313–318.
Rosenthal, R., Megyesi, J.F, Henzei, W.J., Ferrara, N. and Folkman, J. (1990) Conditioned medium from mouse sarcoma 180 cells contains vascular endothelial growth factor. Growth Factors 4:53–59.
Seetharam, L., Gotoh, N., Maru, Y, Neufeld, G., Yamaguchi, S. and Shibuya, M. (1995) A unique signal transduction pathway for the FLT tyrosine kinase, a receptor for vascular endothelial growth factor. Oncogene 10:135–137.
Sellke, EW., Kagaya, Y, Johnson, R.G., Shafique, T., Schoen, F.J., Grossman, W. and Weintraub, R.M. (1993) Endothelial modulation of porcine corinary microcirculation perfused via immature vessels. Am. J. Physiol. 262:h 1669–1695.
Senger, D.R., Galli, S.J., Dvorak, A.M., Perruzzi, CA., Harvey, VS. and Dvorak, H.F. (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites ftuid. Science 219:983–985.
Senger, D., Perruzzi, CA., Feder, J. and Dvorak, H.F. (1986) A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 36:5269–5275.
Shalaby, F., Rossant, J., Yamaguchi, TR, Gertenstein, M., Wu, X.-E, Breitman, M.L. and Schuh, A.C. (1995) Failure of blood island formation and vasculogenesis in Flk-1 deficient mice. Nature 376:62–66.
Shibuya, M., Yamaguchi, S., Yamane, A., Ikada, T., Tojo, T, Matsushima, H. and Sato, M. (1990) Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase (flt) closely related to the fms family. Oncogene 8:519–527.
Shifren, J.L., Doldi, N., Ferrara, N., Mesiano, S. and Jaffe, R.B. (1994) In the human fetus, vascular endothelial growth factor (VEGF) is expressed in epithelial cells and myocytes, but not vascular endothelium: implications for mode of action. J. Clin. Endocrinol. Metab 79:316–322.
Shima, D.T., Adamis, A.P., Ferrara, N., Yeo, K.-T, Yeo, T.K., Folkman, J. and D’Amore, P.A. (1995) Hypoxic induction of vascular endothelial cell growth factors in the retina: Identification and characterization of vascular endothelial growth factor (VEGF) as the sole mitogen. Molec. Med. 2:64–71.
Shweiki, D., Itin, A., Soffer, D. and Keshet, E. (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845.
Shweiki, D., Itin, A., Neufeld, G., Gitay-Goren, H. and Keshet, E. (1993) Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin. Invest. 91:2235–2243.
Sillman, F., Boyce, J. and Fruchter, R. (1981) The significance of atypical vessels and neovascularization in cervical neoplasia. Am. J. Obstet. Gynecol. 139:154–157.
Smith-McCune, K.S., Weidner, N. (1994) Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res. 54:804–808.
Srenath, T., Matrisian, L.M., Stetler-Stevenson, W., Gattoni-Celli, S. and Pozzatti, R.O. (1992) Expression of matrix metalloproteinases in transformed rat cell lines of high and low meta-static potential. Cancer Res. 52:4942–4947.
Srivastava, A., Laidler, P., Davies, R., Horgan, K. and Hughes, L.E. (1988) The prognostic significance of tumor vascularity in intermediate-thickness (0.76–4.00 mm thick) skin melanoma. Am. J. Pathol. 133:419–423.
Takeshita, S., Zhung, L., Brogi, E., Kearney, M., Pu, L.-Q., Bunting, S., Ferrara, N., Symes, J.F. and Isner, J.M. (1994a) Therapeutic angiogenesis: A single intra-arterial bolus of vascular endothelial growth factor augments collateral vessel formation in a rabbit ischemic hindlimb model. J. Clin. Invest. 93:662–670.
Takeshita, S., Pu, L.-Q., Stein, L.A., Sniderman, A.D., Bunting, S., Ferrara, N., Isner, J.M. and Symes, J.F. (1994b) Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation 90:11228–234.
Takeshita, S., Zheng, L.P., Cheng, D., Riessen, R., Weir, L., Symes, J.F, Ferrara, N. and Isner, J.M. (1996) Therapeutic angiogenesis following arterial gene transfer of vascular endothelial in a rabbit model of hind-limb ischemia. Lab. Invest. In press.
Terman, B.I., Carrion, M.E., Kovacs, E., Rasmussen, B.A., Eddy, R.L. and Shows, T.B. (1991) Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene 6:519–524.
Terman, B.I., Vermazen, M.D., Carrion, M.E., Dimitrov, D., Armellino, D.C., Gospodarowicz, D. and Bohlen, P. (1992) Identification of the KDR tyrosine kinase as a receptor for vascular endothelial growth factor. Biochem. Biophys. Res. Commun. 34:1578–1586.
Tisher, E., Mitchell, R., Hartmann, T, Silva, M., Gospodarowicz, D., Fiddes, J. and Abraham, J. (1991) The human gene for vascular endothelial growth factor. J. Biol. Chem. 266: 11947–11954.
Thompson, R.W. and D’Amore, P.A. (1990) Recruitment of growth and collateral circulation. In: G.B. Zelenock, L.G. D’Alecy, J.C, Fantone III, M. Shlafer, J.C. Stanley (eds): Clinical ischemic syndromes: mechanisms and consequences of tissue injury. C.V Mosby, St. Louis, pp 117–137.
Toi, M., Hoshima, S., Takayanagi, T. and Tominaga, T. (1994) Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn. J. Cancer Res. 85:1045–1049.
Tolentino, M.J., Miller, J.W., Gragoudas, E.S., Chatzistefanou, K., Ferrara, N. and Adamis, A.P. (1996) VEGF is sufficient to produce iris neovascularization and neovascular glaucoma in an non-human primate, Ophthalmology. In press.
Topol, E.J. (1996) Textbook of Interventional Cardiology, W.B. Saunders Co., Philadelphia.
Unemori, E., Ferrara, N., Bauer, E.A. and Amento, E.P. (1992) Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells.J Cell. Physiol. 153:557–562.
Vaisman, N., Gospodarowicz, D. and Neufeld, G. (1990) Characterization of the receptors for vascular endothelial growth factor. J. Biol. Chem. 265: 19461–19469.
Vartanian, R.K. and Weidner, N. (1994) Correlation of intramural endothelial cell proliferation with microvessel density (tumor angiogenesis) and tumor cell proliferation. Am. J. Pathol. 144:1188–1194.
Wakui, S., Furusato, M., Sasaki, H., Akiyama, A., Kinoshito, I., Asano, K., Tokuda, T, Aizawa, S. and Ushigome, S. (1992) Tumor angiogenesis in prostatic carcinoma with and without bone metastasis: a morphometric study. J. Pathol. 168:257–262.
Walder, CE., Errett, C.J., Ogez, J., Heinshon, FL, Bunting, S., Lindquist, P., Ferrara, N. and Thomas, G.R. (1996) Vascular endothelial growth factor (VEGF) improves blood flow and function in a chronic ischemic hind-limb model. J. Cardiovasc. Pharmacol 27:91–98.
Waltenberger, J., Claesson-Welsh, L., Siegbahn, A., Shibuya, M. and Heldin, C.H. (1994) Different signal transduction properties of KDR and Fltl, two receptors for vascular endothelial growth factor. J. Biol Chem. 269:26988–26995.
Wand, G.L. and Semenza, G.L. (1995) Purification and characterization of hypoxia-inducible factor-1. J. Biol. Chem. 270:1230–1237.
Wang, G.L., Jiang, B.H., Rue, E.A. and Semenza, G.L. (1995) Hypoxia-inducible factor-1 is a basic helix-loop helix-PAS heterodimer regulated by cellular 02 tension. Proc. Natl. Acad. Sci. USA 92:5510–5514.
Warren, R.S., Yuan, H., Math, M.R., Gillett, N.A. and Ferrara, N. (1995) Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J. Clin. Invest. 95:1789–1797.
Weidner, N., Semple, P., Welch, W. and Folkman, J. (1991) Tumor angiogenesis and metastasis. Correlation in invasive breast carcinoma. N. Engl J. Med. 324:1–6.
Weidner, N., Folkman, J., Pozza, F., Bevilacqua, P., Allred, E.N., Moore, D.H., Meli, S. and Gasparini, G. (1992) Tumor angiogenesis: A new significant and independent prognostic indicator in early-stage breast carcinoma. J. Natl. Cancer Inst. 84:1875–1888.
Wizigmann-Voss, S., Breier, G., Risau, W. and Plate, K. (1994) Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastoma. Cancer Res. 55:1358–1364.
Yang, R., Thomas, G.R., Bunting, S., Ko, A., Keyt, B., Ferrara, N., Ross, J. and Jin, H. (1996) Effects of hemodynamics and cardiac performance. J. Cardiovasc. Pharmacol, 27: 838–844.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Birkhäuser Verlag Basel, Switzerland
About this chapter
Cite this chapter
Ferrara, N., Keyt, B. (1997). Vascular endothelial growth factor: Basic biology and clinical implications. In: Goldberg, I.D., Rosen, E.M. (eds) Regulation of Angiogenesis. Experientia Supplementum, vol 79. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9006-9_9
Download citation
DOI: https://doi.org/10.1007/978-3-0348-9006-9_9
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-9864-5
Online ISBN: 978-3-0348-9006-9
eBook Packages: Springer Book Archive