The authors believe that this finding may explain why expression of integrin-alphaVbeta3 is associated with more aggressive behavior for pancreatic cancers and a host of other tumors. Moreover, testing for this expression may help guide treatment decisions, they add.
Integrins are known to regulate adhesion-dependent growth, but the new findings suggest that integrin-alphaVbeta3 also has an adhesion-independent role, Dr. David A. Cheresh, from the University of California, San Diego, and colleagues note.
In the new study, reported in the September 6th Advance Online issue of Nature Medicine, the researchers found that alphaVbeta3 expression in carcinoma cells was associated with increased anchorage-independent tumor growth in vitro and with greater lymph node metastases in vivo.
Further analysis showed that c-Src recruitment to the beta3 integrin cytoplasmic tail was critical for the effects on tumor growth and lymph node metastases to occur.
Drug blockade of c-Src kinase activity with dasatinib or decreased expression of c-Src or alphaVbeta3 blocked anchorage-independent growth and suppressed metastasis, but had no effect on tumor cell migration or invasion.
"We discovered an unexpected pathway that accounts for increased malignancy in a population of some of the most dangerous cancers," Dr. Cheresh said in a statement. "There are features of the findings that allow us to implicate dasatinib not just for a single tumor type, but for all tumors with the malignant signature."
Nat Med 2009.
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