COMPARATIVE-ANALYSIS OF THE EXPRESSION PATTERNS OF METALLOPROTEINASESAND THEIR INHIBITORS IN BREAST NEOPLASIA, SPORADIC COLORECTAL NEOPLASIA, PULMONARY CARCINOMAS AND MALIGNANT NON-HODGKINS-LYMPHOMAS IN HUMANS

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibito rs of metalloproteinases, TIMPs) play essential roles in the remodelli ng of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of m alignant tumours. In this study we have analysed the expression of fiv e MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions o f human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-11 (stromelysin 3) were most consistently expressed by carcin omas. Based on detection of either MMP-9 or MMP-11 mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequentl y, these results were compared with results for carcinomas of colon an d lung and malignant non-Hodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-11 characteri sed all carcinomas as well as carcinomas in situ but was not detectabl e in NHL. Our data therefore argue that there are remarkably similar p atterns of specific functions involved in ECM remodelling that correla te with malignancy in different human tumours of different histogenesi s. However, MMP-11 expression is a characteristic of tumours of epithe lial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-11 may play a regulatory role in the invasion and metastasis of carcinomas.