Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology.
Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumor development. The distribution of 3 major matrix metallo-proteinases was studied in human mammary pathology: collagenase (MMP1) which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3) which has a wider range of action, degrading several matrix components including the core proteins of proteoglycans, laminin and non-helical regions of collagens. These MMPs and the MMP tissual inhibitor (TIMP1) were detected by immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas: collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a limited distribution. Tumor cells were preferentially labelled and the localization of gelatinase and stromelysin at the periphery of some non-invasive and well-differentiated clusters supports the role of these enzymes in the breakdown of basement membranes. Only a few stromal cells (fibroblasts) were found to be immunopositive. In contrast, TIMP1 was more frequently detected, and was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly localized at the periphery of the endothelial cells but was occasionally detected in cancer cells and fibroblasts.
Clavel
C
C
INSERM U 314-Laboratoire Pol Bouin, Hôpital Maison-Blanche, Reims, France.
Polette
M
M
Doco
M
M
Binninger
I
I
Birembaut
P
P
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology*; D017364:Collagenases / Q000378:metabolism / Q000502:physiology; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged
D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3