Function of the Stroma-Derived Metalloproteinase, Stromelysin-3, in Invasive Breast Carcinomas.
Abstract
Stromelysin-3 (ST-3), a member of the matrix metalloproteinase (MMP) family, is expressed in stromal cells surrounding invasive breast carcinoma cells. where it undergoes processing to its active form by an intracellular, proprotein convertase-dependent pathway. While strong correlations between disease progression and ST-3 expression suggest that the proteinase plays a critical role in breast cancer, human ST-3 is the only matrix metalloproteinase that does not express a marked ability to degrade components of the extracellular matrix (ECM). To further characterize the role of ST-3 in vivo, our attention focused on the analysis of lines of transgenic mice wherein the whey acidic protein (WAP) gene was used to direct human ST-3 expression to mammary tissue during late pregnancy through lactation. In these studies, high levels of the ST-3 transgene were generated in vivo which unexpectedly triggered a massive involution program. Surprisingly, ST-3 not only induced an apoptotic program, but also initiated changes in the underlying basement membrane in vivo. In addition, ST-3 expression also appeared to induce an exaggerated angiogenic response in involuting tissues. These data provide the first evidence that ST-3 can regulate mammary epithelial- ECM interactions and angiogenesis in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA358458
Entities
People
- Stephen J. Weiss
Organizations
- University of Michigan