Function of the Stroma-Derived Metalloproteinase, Stromelysin-3, in Invasive Breast Carcinomas.

Stromelysin-3, a new member of the matrix metalloproteinase family, is specifically expressed in stromal cells surrounding invasive breast carcinoma cells where it undergoes processing to its active form by a proprotein convertase-dependent pathway. We now report that stromelysin-3 does not exert direct matrix-degrading activities or alter the expression of an invasive phenotype in vitro. However, following targeted expression of the ST-3 transgene to the lactating mammary gland in vivo, a premature involution program appear to be initiated. Given the fact that matrix remodeling programs induced by breast cancer cells appears similar to those observed during mammary gland involution, these data suggest that ST-3 may play an important, but indirect, role in regulating tissue integrity in vivo. Furthermore, we demonstrate that the proprotein convertase-dependent activation mechanism used for ST-3 processing can be extended to a second breast cancer-associated matrix metalloproteinase, the membrane-type matrix metalloproteinase. Together, these data indicate that proprotein convertases may regulate a series of matrix metalloproteinases whose expression can exert complex effects on matrix remodeling programs associated with carcinoma invasion and metastasis in vivo. Matrix Metalloproteinase,