Integrin alphavbeta6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver

Integrin alphavbeta6 (αvβ6) is correlated with colon cancer progression. To detect the effects of αvβ6 on liver metastasis, the specificity of αvβ6 against the monoclonal antibody (mAb) 2G2 was examined by immunoprecipitation. Integrin αvβ6-immunoreactivity (IR) in liver metastasis tissues (63 cases) and colon carcinoma (358 cases) were examined. These results showed that αvβ6 was specifically recognized by the mAb 2G2, and that rates of αvβ6 positivity in liver metastatic tissues (71.4%, 45/63) were higher than that for primary colon cancer (34.0%, 122/358) (P < 0.01). Patients who were αvβ6-positive had higher liver metastasis rates (17%, 21/122) than those who were αvβ6-negative (only 3%, 7/236) (P < 0.01). To examine the underlying mechanisms associated with αvβ6 regulating colonic metastasis in the liver, experimental liver metastasis (intrasplenic injection of HT29 transfectants) and liver colonization assays (direct injection of WiDr transfectants into the liver) in nude mice were performed; these demonstrated that αvβ6 contributed to the promotion of the metastatic potential and the survival of cancer cells in the liver. Matrix metalloproteinase-9 (MMP-9) levels in the cultures of both HT29 and WiDr cells were detected by the Biotrak MMP-9 activity assay system and gelatin zymography assay, and showed that suppression of αvβ6-IR inhibited MMP-9 activity and secretion. Transwell migration assay in vitro also showed that αvβ6 promoted migration on fibronectin for HT29/WiDr mock compared with HT29/WiDr antisense β6 transfects (P < 0.01). We concluded that αvβ6 may mediate the potential for colon cancer cells to colonize in and metastasize to the liver. The mechanisms that αvβ6 may be involved in include the promotion of MMP-9 secretion, the enhancement of migration on fibronectin, and the survival of cancer cells in the liver. (Cancer Sci 2008; 99: 879–887)