DETECTION AND LOCALIZATION OF MESSENGER-RNAS ENCODING MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITOR IN HUMAN BREAST PATHOLOGY

Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective-tissue-matrix remodelling and t he accelerated breakdown associated with tumor development. These MMPs and tissue inhibitor of MMPs (TIMP1) could be expressed by either the cancer or the stromal cells. Expression of mRNAs encoding interstitia l collagenase (MMP1), 72-kD type IV collagenase (MMP2) and stromelysin (MMP3), which are probably involved in tumor invasion and metastasis, and of TIMP1 were studied in human mammary pathology by in situ hybri dization and Northern blot analysis. Out of 6 benign lesions, 2 expres sed MMP2 mRNAs. mRNAs encoding MMP1 and MMP3 were detectable in occasi onal stromal and tumor cells in 2 out of 17 carcinomas. Thirteen out o f 17 cancers expressed MMP2 mRNA throughout the tumor in stromal cells close to noninvasive tumor clusters and well-differentiated invasive cancer cells. TIMP1 mRNA expression was detected in noninvasive and we ll-differentiated invasive tumor cells. These data suggest that there is a cooperation between tumor and stromal cells, in particular for th e production of 72-kD type IV collagenase, involved in the disruption of basement membranes. A lack of TIMP1 expression from invasive cancer cells would also contribute to matrix destruction.