Abstract
All through the 1970s the long search for an elusive angiogenic factor has caused skepticism for the concept proposed by Folkman (1972) that tumors secrete promoters of angiogenesis. In 1983 Folkman and his colleagues have succeeded in isolating a heparin binding factor and a year later Guilleman’s laboratory described the amino acid sequence of b-FGF (Folkman, 1985). Today we have numerous factors that have been reported to either promote or suppress angiogenesis. Many of them have been sequenced and their genes cloned. A partial list of angiogenic substances are shown in Table 1. The relative contribution of these factors in the control of physiological and pathological angiogenesis remains to be elucidated. All the angiogenic factors listed in Table 1 do not satisfy to the same extent the critiria for an in vivo angiogenic factor such as VEGF. For VEGF it has been shown that it specifically stimulates mitogenic activity and invasion into extracellular matrix and tube formation of endothelial cells only. In addition VEGF promotes angiogenesis in vivo and there is a temporal and spatial formation of VEGF in all types of angiogenesis (embryonic, ovulation and cancer). m-RNA for the receptor of VEGF and binding to the receptor during angiogenesis is demonstrated only in the proliferating endothelial cells. Furthemore, inhibition of the production of VEGF or the expression of the receptor leads to inhibition of angiogenesis and tumor growth.
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References
Amezcua, J.L., Palmer, R.M.J., De Souza, B.M. and Moncada, S., 1989, Nitric oxide synthesized from L-arginine regulates vascular tone in the coronary circulation of the rabbit, Br. J. Pharmacol., 97:1119–1124.
Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y., 1982, Direct activation of calcium activated, phospholipid dependent protein kinase by tumor promoting phorbol esters, J. Biol. Chem., 257:7847–7851.
Cohen, P., 1992, Signal integration at the level of protein kinases, protein phosphateses and their substrates, TIBS, 17:408–413.
Cui, S.J., Reichner, J.S., Mateo, R.B., and Albina, J.E., 1994, Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or -independent mechanisms, Cancer Res., 54:2462–2467.
Dong, Z.Y., Starolesky, A.H., Qi, X.X., Xie, K.P., and Fidler, I.J., 1994, Inverse correlation between expression of nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. Cancer Res., 54:789–793.
Folkman J., 1972, Anti-angiogenesis: New concept for therapy of solid tumors, Ann. Surg., 409–416.
Folkman, J., 1985, Towards an understanding of angiogenesis, Search and Discovery, Prospect. Biol. Med. 29:10–35.
Folkman, J. and Shing, Y., 1992, Angiogenesis: Minireview, J. Biol. Chem., 267:10931–10932.
Folkman, J., 1995, Angiogenesis in cancer, vascular, rheumatoid and other disease, Nature Medicine 1:27–31.
Forstermann, U., Schmidt, H.H.H.W., Pollock, J.S., Sheng, H., Mitchell, J.A., Warner, T.D., Nakane, M. & Murad, F.,1991, Commentary. Isoforms of nitric oxide synthase. Characterization and purification from different cell types, Biochem. Pharmacol., 42(10): 1849–1857.
Iwamoto, Y., Koide, H., Ogita, K., and Nishizuka, Y., 1992, The protein kinase C family for the regulation of cellular functions, Bio Med. Reviews, 1:1–6.
Gopalakrishna, R., Hai Chen, Z., and Gundimeda, U., 1993, Nitric oxide and nitric oxide generating agents induce a reversible activation of protein kinase C activity and phorbol ester binding, J. Biol. Chem., 268:27180–27185.
Hannun, Y.A., Foflesong, RJ., and Bell, R.M., 1989, The adriamycin-iron (III) complex is a potent inhibitor of protein kinase C. J. Biol. Chem., 264:9960–9966.
Haralabopoulos, G.C., Grant, D.S., Kleinman, H.K., Lelkes, P.I., Papaioannou, S.P. and Maragoudakis, M.E., 1994, Inhibitors of basement collagen biosynthesis prevent endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. Lab. Invest. 71(4):575–582.
Hibbs, J.B., Taintor, R.R, Vavrin, Z., and Rachlin, E.M., 1988, Nitric oxide: A cytotoxic activated macrophage effector molecule, Biochem. Biophys. Res. Commun., 157:87–94.
Houslay, M.D., 1991, “Crosstalk”: A pivotal role of protein kinase C in modulating relationships between signal transduction pathways, Eur. J. Biochem., 195:9–27.
Knowles, R.G., Moncada, S., 1992, Nitric oxide as a signal in blood vessels, TIBS 17:399–402.
Maeda, H., Noguchi, Y., Sato, K., and Akaike, T., 1994, Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor, Japan. J. Cancer Res., 85:331–334.
Mantley, C. L., Perera, P.Y., Salkowski, CA., and Vogel, S.N., 1994, Taxol provides a second signal for murine macrophages tumoricidal activity, J. Immunol., 152: 825–831
Maragoudakis, M.E., Sarmonika, M., Panoutsakopoulou, M, 1988, Inhibition of basement membrane biosynthesis prevent angiogenesis, J. Pharm. & Exper. Ther., 244:729–733.
Maragoudakis, M.E., Sarmonika, M., and Panoutsakopoulou, M., 1988, Rate of basement membrne biosynthesis as an index to angiogenesis, Tissue & Cell, 20 (4):531–539.
Mayer, B., Schmidt, K., Humbert, P., and Bohme, E., 1989, Biosynthesis of endothelium derived relaxing factor: a cytosolic enzyme in porcine aortic endothelial cells Ca++ dependently converts L-arginine into an activator of soluble guanylate cyclase, Biochem. Biophys. Res. Commun. 164:678–685.
Nakaki, T., Makayama, M., and Kto, R., 1990, Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells, Eur. I. Pharmacol., 189:347–353.
O’Brian, C.A.,Housey, G.M., and Weinstein, LB., 1988, Specific and direct binding of protein kinase C to an immobilized tamoxifen analog, Cancer Res. 48:3626–3629.
Oshima, H., and Barsch, H., 1994, Chronic inflammatory processes as cancer risk factors. Possible role of nitric oxide in carcinogenesis, Mutation Res., 305:253–264.
Palmer, R.M.J., Ashton, D.S., and Moncada, S., 1988, Vascular endothelial cells synthesize nitric oxide from L-arginine, Nature (Lond.), 333:664–666.
Pipili-Synetos, E., Sakkoula, E., Haralabopoulos, G., Andriopoulou, P., Peristeris P., and Maragoudakis, M.E, 1994, Evidence that nitric oxide is an endogenous antiangiogenic mediator, Br. J. Pharmacol., 111:194–202.
Pipili-Synetos, E., Papageorgiou, G., Sakkoula, E., Sotiropoulou, G., Fotsis, T., Karakiulakis, G., and Maragoudakis, M.E., 1995, Inhibition of angiogenesis, tumor growth and metastasis by the NO-releasing vasodilators, isosorbide mononitrate and dinitrate, Br. J. Pharmacol., 116:1829–1834.
Powiss, G., 1991, Signalling targets for anticancer drug development. Trends in Pharm. Sci., 12:188–194.
Radomski, M.W., Palmer, R.M.J., and Moncada, S., 1990, An L-arginine/nitric oxide pathway present in human platelets regulates aggregation, Proc. Natl. Acad. Sci. U.S.A., 87:5193–5197.
Schmidt, H.H.H.W., 1992, NO., CO and OH, Endogenous soluble guanylate cyclase-activating factors, FEBS Leiters, 307 (1):102–107.
Schmidt, H.H.H.W., Lohman, S., and Walter, U., 1993, Minireview, The nitric oxide and c GMP signal transduction system: regulation and mechanism of action, Biochim. Biophys. Acta 1178:153–175.
Severn, A., Wakelam, M.J.O., Liew, F.Y., 1992, The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages, Biochim. Biophys. Res. Com. 188:997–1002.
Snyder, S.H., and Bredt, D.S., 1992, Biological roles of nitric oxide, Scientific American, May, 28–35.
Tsopanoglou, N.E., Pipili-Synetos, E., and Maragoudakis, M.E., 1993, Thrombin promotes angiogenesis by a mechanism independent of fibrin formation, Am. J. Physiol. 264 (Cell Physiol. 33):C1302–1307.
Tsopanoglou, N.E., Pipili-Synetos E. and Maragoudakis, M.E., 1993, Protein kinase C involvement in the regulation of angiogenesis. J. Vasc. Res., 30:202–208.
Tsopanoglou, N.E., Haralabopoulos, G.C., and Maragoudakis, M.E., 1993, Opposing effects on modulation of angiogenesis by protein kinase C and cyclic AMP-mediated pathways. J. Vasc. Res. 31:195–204.
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© 1996 Plenum Press, New York
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Maragoudakis, M.E. (1996). Signal Transduction Pathways and the Regulation of Angiogenesis. In: Maragoudakis, M.E. (eds) Molecular, Cellular, and Clinical Aspects of Angiogenesis. NATO ASI Series, vol 285. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0389-3_11
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DOI: https://doi.org/10.1007/978-1-4613-0389-3_11
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