Integrin α2 Mediates Selective Metastasis to the Liver

Cancers display distinct patterns of organ-specific metastasis. Comparative analysis of a broad array of cell membrane molecules on a liver-metastasizing subline of B16 melanoma versus the parental B16-F0 revealed unique up-regulation of integrin alpha 2. The direct role of integrin alpha 2 in hepatic metastasis was shown by comparison of high versus low-expressing populations, antibody blockade, and ectopic expression. Integrin alpha 2-mediated binding to collagen type IV (highly exposed in the liver sinusoids) and collagen type IV-dependent activation of focal adhesion kinase are both known to be important in the metastatic process. Analysis of primary colorectal cancers as well as coexisting liver and lung metastases from individual patients suggests that integrin alpha 2 expression contributes to liver metastasis in human colorectal cancer. These findings define integrin alpha 2 as a molecule conferring selective potential for formation of hepatic metastasis, as well as a possible target to prevent their formation. [Cancer Res 2009;69(18):7320-8]