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Integrin alphavbeta6 (α α α αvβ β β β6) is correlated with colon cancer progression. To detect the effects of α α α αvβ β β β6 on liver metastasis, the specificity of α α α αvβ β β β6 against the monoclonal antibody (mAb) 2G2 was examined by immunoprecipitation. Integrin α α α αvβ β β β6-immunoreactivity (IR) in liver metastasis tissues (63 cases) and colon carcinoma (358 cases) were examined. These results showed that α α α αvβ β β β6 was specifically recognized by the mAb 2G2, and that rates of α α α αvβ β β β6 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 α α α αvβ β β β6-positive had higher liver metastasis rates (17%, 21/ 122) than those who were α α α αvβ β β β6-negative (only 3%, 7/236) (P < 0.01). To examine the underlying mechanisms associated with α α α αvβ β β β6 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 α α α αvβ β β β6 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 α α α αvβ β β β6-IR inhibited MMP-9 activity and secretion. Transwell migration assay in vitro also showed that α α α αvβ β β β6 promoted migration on fibronectin for HT29/WiDr mock compared with HT29/WiDr antisense β β β β6 transfects (P < 0.01). We concluded that α α α αvβ β β β6 may mediate the potential for colon cancer cells to colonize in and metastasize to the liver. The mechanisms that α α α αvβ β β β6 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) D espite welcome declines in the mortality rate over the past decade, the prevention of colonic metastasis to the liver in patients with colon carcinoma remains one of the most challenging issues in cancer research. Surgical resection can provide a potentially curative outcome, but nearly a quarter of patients with colon carcinoma will develop a recurrence in the first 5 years, with about 40-50% accounting for liver metastasis.(1) The conventional paradigm of liver metastasis in colon cancer is based on a multistep tumor genesis model defined by a series of progressive somatic genetic alterations, which give malignant cells the ability to proceed through the many phases of metastasis. When a colon carcinoma in situ develops into a metastatic tumor in the liver, the degradation of extracellular matrix (ECM) barriers by matrix metalloproteinase-9 (MMP-9), cell migratory capability, and survival in a new environment, play important roles in facilitating tumor cellular dissemination and...

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The results suggested that Astragaloside II is a potent MDR reversal agent and may be a potential adjunctive agent for hepatic cancer chemotherapy.