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World J Gastroenterol 2003;9(6):1144-1155 World Journal of Gastroenterology Copyright © 2003 by The WJG Press ISSN 1007-9327


Mechanism and its regulation of tumor-induced angiogenesis
Manoj Kumar Gupta, Ren-Yi Qin
Manoj Kumar Gupta, Ren-Yi Qin, Department of Surgery, TongjiHospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China Supported by National Natural Science Foundation of China, No 30271473 Correspondence to: Professor Ren-Yi Qin, Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China. Telephone:+86-27-83662389 Received: 2002-11-29 Accepted: 2003-01-13

Tumor angiogenesis is the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products. The process of angiogenesis plays an important role in many physiological and pathological conditions. Solid tumors depend on angiogenesis for growth and metastasisin a hostile environment. In the prevascular phase, the tumor is rarely larger than 2 to 3 mm3 and may contain a million or more cells. Up to this size, tumor cells can obtain the necessary oxygen and nutrient supplies required for growth and survival by simple passive diffusion. The properties of tumors to release and induce several angiogenic and antiangiogenic factors which play crucial rolesin regulating endothelial cell (EC) proliferation, migration, apoptosis or survival, cell-cell and cell-matrix adhesion through different intracellular signaling are thought to be the essential mechanisms during tumor-induced angiogenesis. Tumor angiogenesis actually starts with tumor cells releasing molecules that send signals to surrounding normal host tissue. This signaling activates certaingenes in the host tissue that, in turn, make proteins to encourage growth of new blood vessels. In this review, we focus the mechanisms of tumor-induced angiogenesis, with an emphasis on the regulatory role of several angiogenic and anti-angiogenic agents during the angiogenic process in tumors. Advances in understanding the mechanisms of tumor angiogenesis have led to the development of severalmost effective antiangiogenic and anti-metastatic therapeutic agents and also have provided several techniques for the regulation of cancer’s angiogenic switch. The suggestion is made that standard cytotoxic chemotherapy and angiogenesis inhibitors used in combination may produce complementary therapeutic benefits in the treatment of cancer.
Gupta MK, Qin RY. Mechanism and its regulation oftumor-induced angiogenesis. World J Gastroenterol 2003; 9(6): 1144-1155

proliferation at the migrating tip; (4) lumen formation, generation of new basement membrane with the recruitment of pericyte, formation of anastomoses and finally blood flow[1]. The angiogenic response in the microvasculature is associated with changes in cellular adhesive interactions between adjacent ECs, pericytes andsurrounding ECM. In the process of active neovascularization, activated ECs reorganize their cytoskeleton, express cell surface adhesion molecules such as integrins and selectins, secrete proteolytic enzymes, and remodel their adjacent ECM. These events are followed by the formation of capillary buds. Autocrine and/or paracrine angiogenic factors must be present to induce EC migration, proliferation,elongation, orientation and differentiation leading to the re-establishment of the basement membrane, lumen formation and anastomosis with other new or pre-existing vessels, eventually leading to the formation of intact microvessels.

MECHANISM OF ANGIOGENESIS Angiogenesis is a complex multi-step process involving extensive interplay between cells,...
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