Overexpression of beta3/gamma2 chains of laminin-5 and MMP7 in biliary cancer.
OBJECTIVE
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.


CONCLUSIONS
Our results suggest that LNgamma2 and LNbeta3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.
Oka
Toshikuni
T
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
Yamamoto
Hiroyuki
H
Sasaki
Shigeru
S
Ii
Masanori
M
Hizaki
Keiichi
K
Taniguchi
Hiroaki
H
Adachi
Yasushi
Y
Imai
Kohzoh
K
Shinomura
Yasuhisa
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D007797:Laminin; D020783:Matrix Metalloproteinase 7; D034741:RNA, Small Interfering; D000097794:Kalinin; C400567:LAMC2 protein, human; C095567:laminin alpha 3; C060932:MMP7 protein, human
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