Aim: To clarify the clinicopathological significance of laminin-5 gamma2 (LNgamma2) and beta3 (LNbeta3) chains and MMP7 expression in biliary tract cancer.
Methods: We analyzed the association between immunohistochemically detected LNgamma2, LNbeta3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed.
Results: LNgamma2 expression was predominantly observed in carcinoma cells at the invasive front. LNgamma2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNbeta3 was classified into two types: invasive front dominant type (38%) and diffuse type (28%). The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNgamma2 or LNbeta3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.
Conclusion: Our results suggest that LNgamma2 and LNbeta3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.