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Expression of Matrix Metalloproteinase-2 and -9 and Tissue Inhibitor of Metalloproteinase-1 and -2 in Intraductal and Nonintraductal Growth Type of Cholangiocarcinoma

Authors
 Kwang Jo Chae  ;  Sun Young Rha  ;  Young Nyun Park  ;  Chanil Park  ;  Jinsub Choi  ;  Young Joo Kim  ;  Ja Seung Koo  ;  Bong-Kyeong Oh 
Citation
 AMERICAN JOURNAL OF GASTROENTEROLOGY, Vol.99(1) : 68-75, 2004 
Journal Title
 AMERICAN JOURNAL OF GASTROENTEROLOGY 
ISSN
 0002-9270 
Issue Date
2004
Abstract
BACKGROUND: The intraductal growth (IG) type of cholangiocarcinoma has a better prognosis than the mass forming (MF) and periductal infiltrating (PI) types. Matrix metalloproteinase (MMP)-2 and MMP-9, regulated by tissue inhibitor of metalloproteinases (TIMP)-2 and TIMP-1, respectively, play important roles in the degradation of the basement membrane during tumor invasion. Alteration in MMPs and TIMPs may regulate the gross morphology of cholangiocarcinoma. METHODS: MMP-2 and MMP-9 were analyzed in 35 cholangiocarcinomas and 4 normal livers with fresh tissue using zymography and real-time reverse transcription-polymerase chain reaction (RT-PCR), and expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 were evaluated in 76 cholangiocarcinomas by immunohistochemistry. RESULTS: Activity of MMP-2 and its active form were detected in 80% and 57% of cholangiocarcinomas respectively. The total MMP-2, active 62 kDa MMP-2, and MMP-2 mRNA increased 5.4 and 8.2 times, 4.4 and 10.9 times, and 2.9 and 5.8 times in the MF and PI types, respectively, compared to the IG type. The majority of MMP-9 was in the proform and active 82 kDa MMP-9 was detected in 9% of cholangiocarcinomas. MMP-9 revealed no significant difference in relation to the gross types. The balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 were significantly decreased in the MF and PI types, compared to the IG type. In the normal and nonneoplastic livers, the expressions of MMP-2 and MMP-9 were very low without active forms. CONCLUSIONS: The activities of MMP-2 and loss of balanced expressions of MMP-2/TIMP-2 and MMP-9/TIMP-1 are suggested as playing important roles in invasive growth related to the gross type of cholangiocarcinoma.
Full Text
http://www.nature.com/ajg/journal/v99/n1/full/ajg200421a.html
DOI
10.1046/j.1572-0241.2003.04025.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Park, Chan Il(박찬일)
Choi, Jin Sub(최진섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111520
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