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Type IV collagen α6 chain‐derived noncollagenous domain 1 (α6(IV)NC1) inhibits angiogenesis and tumor growth
Author(s) -
Mundel Thomas M.,
Yliniemi AnnaMaija,
Maeshima Yohei,
Sugimoto Hikaru,
Kieran Mark,
Kalluri Raghu
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23269
Subject(s) - type iv collagen , angiogenesis , lewis lung carcinoma , basement membrane , matrigel , neovascularization , endogeny , cell growth , angiogenesis inhibitor , cancer research , endocrinology , microbiology and biotechnology , chemistry , biology , laminin , medicine , extracellular matrix , biochemistry , metastasis , cancer
Type IV collagen is a major component of vascular basement membranes. The noncollagenous (NC1) domains of several α‐chains of type IV collagen reveal a capacity to inhibit angiogenesis and tumor growth. Here, we demonstrate that the NC1 domain of the α6 chain of type IV collagen (α6NC1) is an endogenous inhibitor of angiogenesis and tumor growth. Recombinant α6NC1 inhibits human endothelial cell proliferation and neovascularization of Matrigel plugs in mice. The α6NC1 suppresses the growth of subcutaneously transplanted Lewis lung carcinoma and also spontaneous pancreatic insulomas that develop in the Rip1Tag2 mice. Inhibition of tumor growth is associated with significantly diminished microvascular density. Collectively, our results demonstrate that α6NC1 is an endogenous inhibitor of angiogenesis and tumor growth. © 2007 Wiley‐Liss, Inc.