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An angiogenic laminin site and its antagonist bind through the αvβ3 and α5β1 integrins
Author(s) -
Ponce M. Lourdes,
Nomizu Motoyoshi,
Kleinman Hynda K.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0736com
Subject(s) - fibronectin , laminin , integrin , angiogenesis , matrigel , chemistry , peptide , receptor , microbiology and biotechnology , adhesion , extracellular matrix , cancer research , biochemistry , biology , organic chemistry
Angiogenesis is important for wound healing, tumor growth, and metastasis. Endothelial cells differentiate into capillary‐like structures on a laminin‐1‐rich matrix (Matrigel). We previously identified 20 angiogenic sites on laminin‐1 (α1β1γ1) by screening 559 overlapping synthetic peptides. C16, the most potent γ1 chain peptide, blocked laminin‐1‐mediated adhesion and was the only γ1 chain peptide to block attachment to both collagen I and fibronectin. This suggested that C16 was acting via a receptor common to these substrates. We demonstrated that C16 is angiogenic in vivo. Affinity chromatography identified the integrins α5β1 and avβ3 as surface receptors. Blocking antibodies confirmed the role of these receptors in C16 adhesion. C16 does not contain an RGD sequence and, as expected, an RGD‐containing peptide did not block C16 adhesion nor did C16 act via MAP kinase phosphorylation. Furthermore, we identified a C16 scrambled sequence, C16S, which antagonizes the angiogenic activity of bFGF and of C16 by binding to the same receptors. Because the laminin γ1 chain is ubiquitous in most tissues, C16 is likely an important functional site. Since the biological activity of C16 is blocked by a scrambled peptide, C16S may serve as an anti‐angio‐genic therapeutic agent.—Ponce, M. L., Nomizu, M., Kleinman, H. K. An angiogenic laminin site and its antagonist bind through the avβ3 and α5β1 integrins. FASEB J. 15, 1389–1397 (2001)