Relationship between activation of TGF-β1 by αVβ8 integrin and the invasion and metastasis of colorectal cancer

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Relationship between the pattern of the expression of β-catenin and lymphatic metastasis in human colorectal cancers was examined. Paraffin-embedded sections and frozen sections of resected colorectal cancers were stained by antibodies for β-catenin, integrin α3β1, α5β1, β4, αVβ6, β8, TGF-β1, TGF receptor, and thrombospondin. The cases with the nuclear accumulation of β-catenin at the invasion front, showed more increased lymphatic metastases than the membranous or intracytoplasmic staining cases (p=0.0004). Moreover, β8-negative cases showed the more increasing clinical stages and lymphatic metastases. The expression of TGF-β1 and TGF receptor was synchronously observed in about 40% cases. Thrombospondin, which is known as one of activators of TGF-β1, was detected in only 7% cases. Unexpectedly, the expression of integrin β8 and TGF-β1 was not significantly correlated each other in immunohistochemical analyses. The expression of integrin αVβ6 also did not have any correlation with TGF-β1, TGF receptor or β-catenin. In conclusion, down regulation of αVβ8 was not the trigger of the activation of TGF-β1 inducing the accelerated metastatic ability in colorectal cancers.