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a 28 kDa collagen fragment consisting of the NC1 domain of alpha 3 chain of collagen type 4. For similar proteins see also: Arresten, Canstatin, Endostatin, Restin.

The protein has anti-tumor properties and inhibits angiogenesis in an in vivo angiogenesis assay (Matrigel plug assay) (Hamano and Kalluri, 2005). Tumstatin peptides can inhibit the proliferation of endothelial cells in the presence of vitronectin, fibronectin, and collagen type 1. The protein does not affect the migration of these cells (Sudhakar et al, 2003). Tumstatin has been shown to function as an endothelial cell-specific inhibitor of protein synthesis through interaction with integrin-alpha-V / integrin-beta-3 (Maeshima et al, 2001, 2002). Tumstatin has been shown also to promote apoptosis.

Knock-out mice lacking expression of the alpha-3 chain of collagen type 4 show accelerated tumor growth associated with enhanced pathological angiogenesis. Angiogenesis associated with development and tissue repair are unaffected. Increased tumor growth can be abolished by treatment of these mice with recombinant tumstatin. Mice deficient in matrix metalloproteinase-9 (MMP-9), which cleaves tumstatin efficiently from alpha-3 chain of collagen type 4, have decreased circulating tumstatin levels and accelerated tumor growth rates (Hamano et al, 2003).

VBMDMP [Vascular basement membrane-derived multifunctional peptide] is derived from a fusion gene of the human immunoglobulin G3 upper hinge region and two fragments derived from tumstatin. Recombinant VBMDMP blocks the growth and metastatic capacity of Lewis lung carcinoma cells transplanted into C57Bl/6 mice. The protein potently inhibits proliferation of human endothelial cells (HUVEC-12)and human colon cancer cells (SW480) in vitro. It does not inhibit proliferation of Chinese hamster ovary cells. The protein also significantly inhibits human endothelial cell tube formation and suppresses tumor growth of SW480 cells in a mouse xenograft model (Cao et al, 2006).

See also: Angiogenesis Dictionary section of this encyclopedia for other entries directly bearing on factors and processes involved in the generation of new blood vessels.

Copyright 2012 by H IBELGAUFTS. All rights reserved.


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