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
References
1. Офозу, Ф.А. Тромбоциты как модель регуляции свертывания крови на клеточных мембранах и ее значение / Ф.А. Офозу // Биохимия. - 2002. - № 67. - С. 56-65
2. Татосян, А.Г. Киназы семейства Srs: структура и функции / А.Г. Татосян, О.А. Мизенина // Биохимия. - 2000. - № 65(1). - С. 57-67
3. Роль металлопротеиназ матрикса и их ингибиторов в процессах опухолевой инвазии и метастазировании / П.З. Хасигов [и др.] // Биохимия. - 2003. - Т. 68, N 7. - С. 869-876. - ISSN 0320-9725
4. Парфенова, Е.В. Система активаторов плазминогена в ремоделировании сосудов и ангиогенезе / Е.В. Парфенова, О.С. Плеханова, В.А. Ткачук // Биохимия. - 2002. - Т. 67, вып. 1. - С. 139-156
5. Эндостатин: современные представления о его роли и механизмах действия / A.B. Дигтярь [и др.]// Биохимия. - 2007. - Т. 72, № 3. - С. 291-305
6. Folkman, J.,Angiogenesis in cancer, vascular, rheumatoid and other disease / J.Folkman // Nat. Med. - 1995 - №1 - Р. 27-31
7. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. / O’Reilly [et al.] // Cell. - 1997. - Vol.88. - P. 277-285
8. Carmeliet, P. / Angiogenesis in cancer and other diseases / P. Carmeliet, R.K. Jain // Nature. - 2000. - Vol. 407 - P. 249-257
9. Folkman, J. Fundamental concepts of the angiogenic process / J. Folkman - Curr. Mol. Med. - 2003. - Vol. 3. - P. 643-651
10. Nyberg, P. Endogenous inhibitors of angiogenesis / P. Nyberg, L. Xie, R. Kalluri// Cancer Res. - 2005. - Vol. 65 - P. 3967-3979
11. Browder, T. The Hemostatic System as a Regulator of Angiogenesis / T. Browder, J. Folkman, S. Pirie Shepherd // J. Biol. Chem. - 2000. - Vol. 275 - P. 1521-1524
12. Ma, L. Thrombin-induced platelet endostatin release is blocked by a proteinase activated receptor-4 (PAR4) antagonist / L. Ma, M.D. Hollenberg, J.L. Wallace // Br. J. Pharmacol - 2001 - Vol. 134 - P. 701-704
13. Human prothrombin fragment 1 and 2 inhibit bFGF-induced BCE cell growth / Rhim, T.Y. [et al.] // Biochem. Biophys. Res. Commun - 1998 - Vol. 252 - P. 513-516
14. Distinct antitumor properties of a type IV collagen domain derived from basement membrane / Maeshima Y. [et al.] // J Biol Chem - 2000 - Vol. 275 - P. 21340-21348
15. Folkman, J. Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action /J. Folkman, Exp. Cell Res.-2006-Vol. 312-P.594-607
16. Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer / Hansma, A.H. [et al.]// Ann. Oncol. - 2005 - Vol. 16 - P. 1695-1701
17. Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis / Yin G [et al.] // Mol Ther - 2002 - Vol. 5 - P. 547-554
18. Isolation and characterization of the circulating form of human endostatin / Standker L. [et al.] // FEBS Lett. - 1997 - Vol. 420(2-3) - P. 129-133
19. Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution / Hohenester E. [et al.] // EMBO J. - 1998 - Vol. 17(6) - P. 1656-1664
20. Zinc-dependent dimers observed in crystals of human endostatin / Ding, Y.H. // Proc. Natl. Acad. Sci. USA - 1998 - Vol. 95 - P. 10443-10448
21. John H. Determination of the disulfide bond pattern of the endogenous and recombinant angiogenesis inhibitor endostatin by mass spectrometry. Rapid communications in mass spectrometry / H. John, WG.Forssmann // RCM. - 2001 - Vol. 15 - P. 1222-1228
22. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance / T. Boehm [et al.]// Nature - 1997 - Vol. 390 - P. 404-407
23. Folkman, J. Cancer without disease / J.Folkman, R. Kalluri/ Nature - 2004 - Vol. 427 - P. 787
24. Purification and characterization of recombinant murine endostatin in E. coli. / You WK // Exp. Mol. Med. - 1999 - Vol. 31 - P. 197-202
25. Endostatin regulates endothelial cell adhesion and cytoskeletal organization / Dixelius J [et al.]// Cancer Res. - 2002 - Vol. 62 - P. 1944-1947
26. Cloning, expression, and in vitro activity of human endostatin / Dhanabal, M. // Biochem. Biophys. Res. Commun. - 1999 - Vol. 258 - P. 345-352
27. Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1. / Hanai J. [et al.] // J Biol Chem. - 2002 - Vol. 277 - P. 16464-16469
28. Shichiri M. Antiangiogenesis signals by endostatin / MShichiri, Y.Hirata // FASEB J. - 2001 - Vol. 15(6) - P. 1044-1053
29. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins / Sudhakar, A. [et al.] // Proc. Natl. Acad. Sci. USA / 2003 - Vol. 100 - P. 4766-4771
30. A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. / Wary, K.K [et al.] // Cell - 1998 - Vol. 94 - P. 625-634
31. Wickstrom SA. Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells / SAWickstrom, KAlitalo, J.Keski-Oja // Cancer Res. - 2002 - Vol. 62 - P. 5580-5589
32. Thomas, S.M. Cellular functions regulated by Src family kinases / S.M. Thomas, J.S.Brugge // Annu. Rev. Cell Dev. Biol. - 1997 - Vol. 13 - P. 513-609
33. Shattil, S.J. Integrins and Src: dynamic duo of adhesion signaling / S.J. Shattil // TRENDS in Cell Biology - 2005 - Vol. 15 - P. 399-403
34. Role of the cytoplasmic tyrosines of beta 1A integrins in transformation by v-src. / Sakai T. [et al.] // Proc Natl Acad Sci USA - 2001 - Vol. 98 - P. 3808-3813
35. Burridge, K. Focal adhesions, contractility, and signaling / K.Burridge, M.Chrzanowska Wodnicka // Annu. Rev. Cell Dev. Biol. - 1996 - Vol. 12 - P. 463-518
36. Structural basis and potential role of heparin/heparan sulfate binding to the angiogenesis inhibitor endostatin. / Sasaki T. [et al.] // EMBO J. - 1999 - Vol. 18(22) - P. 6240-6248
37. Laminin modulates morphogenic properties of the collagen XVIII endostatin domain. / Javaherian K. [et al.] // J. Biol. Chem. - 2002 - Vol. 277 - P. 45211-45218
38. Endostatin inhibits human tongue carcinoma cell invasion and intravasation and blocks the activation of matrix metalloprotease-2, -9, and -13. / Nyberg P. [et al.] // J Biol Chem. - 2003 - Vol. 278 - P. 22404-22411
39. Generation and degradation of human endostatin proteins by various proteinases / Ferreras, M. [et al.] // FEBS Lett. - 2000 - Vol. 486 - P. 247-251
40. Endostatin-induced modulation of plasminogen activation with concomitant loss of focal adhesions and actin stress fibers in cultured human endothelial cells. / Wickstrom SA [et al.] // Cancer Res. - 2001 - Vol. 61 - P. 6511-6516
41. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase / Kim, Y.M. [et al.] // Cancer Res. - 2000 - Vol. 60 - P. 5410-5413
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.)
Views:
119
Email this article 
