期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 281, 期 30, 页码 20932-20939出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M601147200
关键词
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资金
- NCI NIH HHS [R01-CA94849] Funding Source: Medline
- NIDDK NIH HHS [R01-DK 69921, 5F32 DK065375, R01-DK074359, P01 DK65123, 4R37 DK18381] Funding Source: Medline
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.
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