IMBALANCE OF EXPRESSION OF MATRIX METALLOPROTEINASES (MMPS) AND TISSUE INHIBITORS OF THE MATRIX METALLOPROTEINASES (TIMPS) IN HUMAN PANCREATIC-CARCINOMA

Degradation of the extracellular matrix (ECM) is an essential step in tumour invasion and metastasis. The matrix metalloproteinases (MMPs) e ach have different substrate specificities within the:ECM and are impo rtant in its degradation. MMP activity is dependent on the levels of a ctivated MMP and tissue inhibitors of matrix metalloproteinases (TIMPs ). The expression of MMPs and TIMPs in pancreatic carcinoma, normal pa ncreas, and pancreatic carcinoma cell lines has been determined by Nor thern analysis. The transcripts have been localized by in situ hybridi zation and the MMP2 protein by immunohistochemistry. Expression of MMP 2, -7, and -11 was greater in pancreatic carcinoma than in normal panc reas (P<0.01). MMP7 expression in normal pancreas and MMP7 and -11 exp ression in tumours was always seen with TIMP1 expression. TIMP2 was ex pressed in only half of the tumours and a previously undescribed trans cript size is reported for TIMP2. MTMMP was expressed concurrently,vit h MMP2 in 64 per cent of tumours, but concurrent MMP2 and TIMP2 expres sion occurred in only half. MMP2 mRNA was found more often in the tumo ur stroma than with the other MMPs or TIMPs (P<0.02). It is concluded that while overexpression of MMP7 and -11 mag be countered by TIMP1, t he aggressive phenotype of pancreatic carcinoma may occur because of o verexpression of MMP2, activated by MTMMP and associated with a reduce d expression of TIMP2. (C) 1997 by John Wiley & Sons, Ltd.