MT-MMP EXPRESSION AND LOCALIZATION IN HUMAN LUNG AND BREAST CANCERS

Thirteen primary pulmonary squamous cell carcinomas, 4 specimens of no rmal lung from around tumours, 4 benign proliferations of the mammary gland and 16 breast carcinomas were analysed by in situ hybridisation, Northern blot and immunohistochemistry for the expression of a recent ly described metalloproteinase (MMP), the MT-MMP (membrane-type matrix metalloproteinase). This MT-MMP can activate gelatinase A, involved i n the degradation of basement membranes. In situ hybridisation reveale d MT-MMP transcripts distributed in both tumour and stromal cells in s quamous cell lung cancers, whereas these mRNAs were principally detect ed in stromal cells in close contact to tumour clusters in breast carc inomas and in lung adenocarcinomas. Northern blot analysis showed a pa rallel expression of MT-MMP and gelatinase A transcripts in both lung and breast cancers. Immunohistochemistry displayed a more extensive di stribution of MT-MMP in pulmonary and mammary carcinomas with numerous labelled preinvasive and infiltrating cancer cells and stromal cells near the tumour cells. The large degree of expression of MT-MMP in the se cancers indicates a potential role of this enzyme in tumour progres sion. The finding of MT-MMP transcripts in stromal cells in the vicini ty of lung and breast tumour cells emphasises the cooperation between these cells and cancer cells for the expression of MT-MMP and in tumou r invasion in vivo.