Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Aug 21, 2009; 15(31): 3865-3873
Published online Aug 21, 2009. doi: 10.3748/wjg.15.3865
Overexpression of β3/γ2 chains of laminin-5 and MMP7 in biliary cancer
Toshikuni Oka, Hiroyuki Yamamoto, Shigeru Sasaki, Masanori Ii, Keiichi Hizaki, Hiroaki Taniguchi, Yasushi Adachi, Kohzoh Imai, Yasuhisa Shinomura
Toshikuni Oka, Hiroyuki Yamamoto, Shigeru Sasaki, Masanori Ii, Keiichi Hizaki, Hiroaki Taniguchi, Yasushi Adachi, Yasuhisa Shinomura, First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
Kohzoh Imai, Sapporo Medical University, Sapporo 060-8556, Japan
Author contributions: Oka T and Yamamoto H designed the research; Oka T, Yamamoto H, Sasaki S, Ii M, Hizaki K, Taniguchi H and Adachi Y performed the research; Oka T, Yamamoto H, Imai K and Shinomura Y analyzed the data; Oka T, Yamamoto H and Shinomura Y wrote the paper.
Correspondence to: Hiroyuki Yamamoto, MD, FJSIM, PhD, First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. h-yama@sapmed.ac.jp
Telephone: +81-11-6112111
Fax: +81-11-6112282
Received: May 11, 2009
Revised: July 15, 2009
Accepted: July 22, 2009
Published online: August 21, 2009
Abstract

AIM: To clarify the clinicopathological significance of laminin-5 γ2 (LNγ2) and β3 (LNβ3) chains and MMP7 expression in biliary tract cancer.

METHODS: We analyzed the association between immunohistochemically detected LNγ2, LNβ3, 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: LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 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 LNβ3 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 LNγ2 or LNβ3 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 LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.

Keywords: Biliary tract cancer, Laminin-5, Laminin γ2, Laminin β3, MMP7