Oka Toshikuni, Yamamoto Hiroyuki, Sasaki Shigeru, Ii Masanori, Hizaki Keiichi, Taniguchi Hiroaki, Adachi Yasushi, Imai Kohzoh, Shinomura Yasuhisa
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
World J Gastroenterol. 2009 Aug 21;15(31):3865-73. doi: 10.3748/wjg.15.3865.
To clarify the clinicopathological significance of laminin-5 gamma2 (LNgamma2) and beta3 (LNbeta3) chains and MMP7 expression in biliary tract cancer.
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.
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.
Our results suggest that LNgamma2 and LNbeta3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.
阐明层粘连蛋白-5γ2（LNγ2）和β3（LNβ3）链以及基质金属蛋白酶7（MMP7）在胆道癌中的临床病理意义。
我们分析了免疫组化检测到的胆道癌中LNγ2、LNβ3和MMP7表达与临床病理特征之间的关联。通过酪蛋白酶谱分析MMP7的活性。在用MMP7特异性小干扰RNA（siRNA）处理后进行体外侵袭试验。
LNγ2表达主要见于侵袭前沿的癌细胞。57%的胆道癌患者可见LNγ2表达，且与浸润深度、组织学类型和晚期相关。LNβ3的表达模式分为两种类型：侵袭前沿优势型（38%）和弥漫型（28%）。侵袭前沿优势型与组织学类型和晚期相关。MMP7阳性与LNγ2或LNβ3表达相关，但与临床病理特征无关。通过酪蛋白酶谱检测到的活性MMP7与浸润深度和晚期相关。用siRNA下调MMP7表达导致体外胆道癌细胞侵袭显著减少。
我们的结果表明，LNγ2和LNβ3与MMP7共同在胆道癌进展中起关键作用。
