Collagen-Induced Invasion in Breast Cancer.
Abstract
Matrix metalloproteinase-2 (MMP-2) has been implicated in the progression of tumor invasion and metastasis. We have previously demonstrated that, in contrast with non-invasive cell lines, invasive breast cancer cells can activate exogenous MMP-2 when cultivated on collagen I gels. Although the a2beta1 intergrin heterodimer is the principle cellular receptor for collagen type I, we were unable to block the collagen-induced activation of MMP-2 with antibodies against these integrin subunits. However, our experiments identified an exogenous serum factor whose presence was necessary for MMP-2 activation. We demonstrated a correlation between the invasive phenotype and the expression of osteonectin/secreted protein, acidic and rich in cysteine (SPARC). For invasive, but not non-invasive cells, recombinant SPARC (rSPARC) was able to induce MMP-2 activation in serum free medium and this activation was potentiated by exposure to collagen type I. We identified the peptide domain in SPARC responsible for this activity as localized to the N-terminal domain of the protein. Since rSPARC did not effect expression levels or post-translational modifications of MTl-MMP, the mechanism by which it activates MMP-2 remains to be elucidated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA358110
Entities
People
- Emma Bowden
Organizations
- Georgetown University