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Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma

โœ Scribed by Bramhall, Simon R.; Neoptolemos, John P.; Stamp, Gordon W. H.; Lemoine, Nicholas R.


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
459 KB
Volume
182
Category
Article
ISSN
0022-3417

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โœฆ Synopsis


Degradation of the extracellular matrix (ECM) is an essential step in tumour invasion and metastasis. The matrix metalloproteinases (MMPs) each have different substrate specificities within the ECM and are important in its degradation. MMP activity is dependent on the levels of activated MMP and tissue inhibitors of matrix metalloproteinases (TIMPs). The expression of MMPs and TIMPs in pancreatic carcinoma, normal pancreas, and pancreatic carcinoma cell lines has been determined by Northern analysis. The transcripts have been localized by in situ hybridization and the MMP2 protein by immunohistochemistry. Expression of MMP2, -7, and -11 was greater in pancreatic carcinoma than in normal pancreas (P<0โ€ข01). MMP7 expression in normal pancreas and MMP7 and -11 expression in tumours was always seen with TIMP1 expression. TIMP2 was expressed in only half of the tumours and a previously undescribed transcript size is reported for TIMP2. MTMMP was expressed concurrently with MMP2 in 64 per cent of tumours, but concurrent MMP2 and TIMP2 expression occurred in only half. MMP2 mRNA was found more often in the tumour stroma than with the other MMPs or TIMPs (P<0โ€ข02). It is concluded that while overexpression of MMP7 and -11 may be countered by TIMP1, the aggressive phenotype of pancreatic carcinoma may occur because of overexpression of MMP2, activated by MTMMP and associated with a reduced expression of TIMP2. 1997 by John Wiley & Sons, Ltd.


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