Abstract
Phorbol esters induce many effects in the cell via activation of protein kinase C (PKC) (Castange et al, 1982) and promote tumor formation (Niedel et al, 1983; Blumberg, 1980). The exact mechanism of tumor promotion is not understood. It has been suggested that stimulation of angiogenesis might be responsible for this effect (Rifkin et al., 1981). Indeed, studies in the chick chorioallantoic membrane (CAM) system have shown that 4-ß-Phorbol-12-myristate-13-acetate (PMA) induced angiogenesis (Morris et al, 1988; Maragoudakis, 1992) and angiogenesis is considered an essential step for growth and metastasis of solid tumors (Folkman, 1985). This angiogenic effect of PMA was attributed by Morris et al. (1988) to the release of angiogenic factors rather than direct stimulation of endothelial cell proliferation.
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References
Blumberg, P.M., 1980, In vitro studies on the mode of action of the phorbol esters, potent tumor promoters. CRC Crit. Rev. Toxicol. 8:199–234.
Boni, L.T., and Rando, R.R., 1985, The nature of protein kinase C activation by physically defined phospho-lipid vesicles and diacylglycerols. J. Biol. Chem. 260:1081910825.
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. 257:7845–7851.
Davis, P.D., Hill, C.H., Keech, E., Lawton, G., Nixon, J.S., Sedgwick, A.D., Wadsworth, J., Westmacott, D., and Wilkinson, S.E., 1989, Potent selective inhibitors of protein kinase C. FEBS Lett. 259(1): 61–63.
Folkman, J., 1983, Tumor angiogenesis. Adv. Cancer Res. 43:172–203.
Harris-Hooker, S. A., Gajdusek, S. M.,Wight, T. N. and Schwartz, S. M., 1983, Neo vascularization responses induced by cultured aortic endothelial cells. J. Cell Physiol. 114:302–310.
Hidaka, H., Inagaki, M., Kawamoto, S.and Susaki, Y., 1984, Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry 23:5036–5041.
Linden, D.J., and Connor, JA., 1991, Participation of postsynaptic PKC in cerebellar long-term depression in culture. Science 254:1656–1659.
Maragoudakis, M.E., 1992, Basement membrane biosynthesis as a target for developing angiogenesis inhibitors with antitumor properties. ln: Cell and Molecular Biology of Basement Membranes in Health and Disease. N. Kefalides, ed., Kidney International (in press).
Maragoudakis, M.E., Panoutsacopoulou, M. and Sarmonika, M., 1988, Rate of basement membrane biosynthesis as an index to angiogenesis. Tissue and Cell 20(4):531–539.
Maragoudakis, M.E., Missirlis, E., Sarmonika, M., Panoutsacopoulou, M. and Karakiulakis, G., 1990, Basement membrane biosynthesis as a target to tumor therapy. J. Pharmacol. Exp. Ther. 252:753–757.
Morris, P.B., Hida, T., Blackshear, P.J., Klintworth, G.K, Swain, J.L., 1988, Tumor promoting phorbol esters induce angiogenesis in vivo. Am. J. Physiol. 23:C318–C322.
Müller-Decker, K., 1989, Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: Inhibition of a phospholipase C type reaction. Biochem. Biophys. Res. Commun. 162:198–205.
Niedel, J.E., Kuhn, L.J., and Vanderbank, G.R., 1983, Phorbol diester receptor copurifies with protein kinase C. Proc. Natl. Acad. Sci., USA 80: 36–40.
Rifkin, D.B., Gross, D., Moscatelli, D., and Gabrieledes, C., 1981, The involvement of poteases and protease inhibitors in neovascularization. Acta Biol. Med. Cer. 40:1259–1263.
Tsopanoglou, N.E., Pipili-Synetos, E., and Maragoudakis, M.E. Thrombin promotes angiogenesis by a mechanism independent of fibrin formation Am. J. Physiology (in press).
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© 1993 Springer Science+Business Media New York
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Maragoudakis, M.E., Tsopanoglou, N.E., Haralabopoulos, G. (1993). Regulation of Angiogenesis Via Protein Kinase C. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 257. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2437-3_7
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DOI: https://doi.org/10.1007/978-1-4615-2437-3_7
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