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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

Borza, Corina M.; Pozzi, Ambra; Borza, Dorin-Bogdan; Pedchenko, Vadim; Hellmark, Thomas LU ; Hudson, Billy G. and Zent, Roy (2006) In Journal of Biological Chemistry 281(30). p.20932-20939
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
30
pages
20932 - 20939
publisher
ASBMB
external identifiers
  • wos:000239187300030
  • scopus:33746325825
ISSN
1083-351X
DOI
10.1074/jbc.M601147200
language
English
LU publication?
yes
id
d0450e74-f498-4c38-8730-d804698c7534 (old id 401338)
date added to LUP
2007-10-01 08:49:02
date last changed
2019-03-19 01:48:25
@article{d0450e74-f498-4c38-8730-d804698c7534,
  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.},
  author       = {Borza, Corina M. and Pozzi, Ambra and Borza, Dorin-Bogdan and Pedchenko, Vadim and Hellmark, Thomas and Hudson, Billy G. and Zent, Roy},
  issn         = {1083-351X},
  language     = {eng},
  number       = {30},
  pages        = {20932--20939},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {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},
  url          = {http://dx.doi.org/10.1074/jbc.M601147200},
  volume       = {281},
  year         = {2006},
}