Integrin alpha 3 beta 1, a Novel Receptor for alpha 3(IV) noncollagenous domain and a trans-dominant inhibitor for integrin alpha v beta 3

Corina M. Borza, Ambra Pozzi, Dorin-Bogdan Borza, Vadim Pedchenko, Thomas Hellmark, Billy G. Hudson, Roy Zent

Research output: Contribution to journalArticlepeer-review

52 Citations (SciVal)

Abstract

Exogenous soluble human alpha 3 noncollagenous (NC1) domain of collagen IV inhibits angiogenesis and tumor growth. These biological functions are attributed to the binding of alpha 3NC1 to integrin alpha v beta 3. However, in some tumor cells that express integrin alpha v beta 3, the alpha 3NC1 domain does not inhibit proliferation, suggesting that integrin alpha v beta 3 expression is not sufficient to mediate the anti-tumorigenic activity of this domain. Therefore, in the present study, we searched for novel binding receptors for the soluble alpha 3NC1 domain in cells lacking alpha v beta 3 integrin. In these cells, soluble alpha 3NC1 bound integrin alpha 3 beta 1; however, unlike alpha v beta 3, alpha 3 beta 1 integrin did not mediate cell adhesion to immobilized alpha 3NC1 domain. Interestingly, in cells lacking integrin alpha 3 beta 1, adhesion to the alpha 3NC1 domain was enhanced due to activation of integrin alpha v beta 3. These findings indicate that integrin alpha 3 beta 1 is a receptor for the alpha 3NC1 domain and transdominantly inhibits integrin alpha v beta 3 activation. Thus integrin alpha 3 beta 1, in conjunction with integrin alpha v beta 3, modulates cellular responses to the alpha 3NC1 domain, which may be pivotal in the mechanism underpinning its anti-angiogenic and anti-tumorigenic activities.
Original languageEnglish
Pages (from-to)20932-20939
JournalJournal of Biological Chemistry
Volume281
Issue number30
DOIs
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Urology and Nephrology

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