MT-MMP expression and localisation in human lung and breast cancers

Thirteen primary pulmonary squamous cell carcinomas, 4 specimens of normal 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 recently described metalloproteinase (MMP), the MT-MMP (membrane-type matrix metalloproteinase). This MT-MMP can activate gelatinase A, involved in the degradation of basement membranes. In situ hybridisation revealed MT-MMP transcripts distributed in both tumour and stromal cells in squamous cell lung cancers, whereas these mRNAs were principally detected in stromal cells in close contact to tumour clusters in breast carcinomas and in lung adenocarcinomas. Northern blot analysis showed a parallel expression of MT-MMP and gelatinase A transcripts in both lung and breast cancers. Immunohistochemistry displayed a more extensive distribution 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 these cancers indicates a potential role of this enzyme in tumour progression. The finding of MT-MMP transcripts in stromal cells in the vicinity of lung and breast tumour cells emphasises the cooperation between these cells and cancer cells for the expression of MT-MMP and in tumour invasion in vivo.