MODERN CONCEPTS ABOUT BIOLOGICAL ROLE AND MECHANISMS OF ACTION OF ENDOSTATIN
Abstract
This review aimed to summarize the results of numerous research of biological activity and mechanism of action of endostatin. Endogenic inhibitors of angiogenesis is one of the main factors of prevention progression of transformation to clinically manifested stages of human cancers. The most potent native inhibitors of angiogenesis and tumor growth is endostatin - a 20- kD protein that is proteolytically released from his parent molecule, collagen XVIII. Endostatin specifically inhibits endothelial cell proliferation both in vitro and in vivo and induces their apoptosis by inhibition of cyclin D1. On the surface of endothelial cells endostatin binds with integrin α5β1, which leads to activation of Src-dependent phosphorylation of p190RhoGAP with concomitant down-regulation of RhoA activity and suppression of the Ras- and Raf-dependent pathways. All this promotes disassembly of actin stress fibers, disruption of cell-matrix interactions, and inhibition of cell migration, in other words, suppresses angiogenesis. In vivo, endostatin displays a potent antitumor activity and inhibits growth and metastasis of more than 60 different tumors.Further research is needed to identify the efficacy of using of endostatin in tumors, particularly in colorectal cancer.
About the Authors
E. T. Idiiatullina
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
V. N. Pavlov
ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России
Russian Federation
Russian Federation
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Review
For citations:
Idiiatullina E.T., Pavlov V.N. MODERN CONCEPTS ABOUT BIOLOGICAL ROLE AND MECHANISMS OF ACTION OF ENDOSTATIN. Bashkortostan Medical Journal. 2017;12(6):126-130. (In Russ.)
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