Relationship Between Scavenger Receptors and UPA:PAI-l and UPA Receptors in Breast Cancer
Abstract
This proposal focuses on the question whether a derangement in expression or trafficking of scavenger receptors, LRP and megalin, might alter their interaction with uPAR, uPA, and PAI-1 in breast cancer cells. We established cell systems and prepared several essential reagents (antibodies) to evaluate the levels of scavenger receptor expression in three estrogen-insensitive and one sensitive breast cell lines, one normal mammary cell line, and a human fibrosarcoma cell line. Our novel findings demonstrate: 1) Differences in the level of expression and distribution of scavenger receptors, uPAR, uPA, and PAI-1 in normal vs. tumor cells. The increased expression of uPAR and uPA in cancer cells mimics the situation in vivo in breast carcinomas where overexpression of uPAR and uPA is associated with poor prognosis; 2) Surface uPAR and LRP colocalize into a molecular complex and are co-internalized via clathrin-mediated endocytosis; 3) Direct interaction between the two receptors stabilizes these complexes even after dissociation of uPA:PAl-i in early endosomes; 4) LRP-dependent clearance of uPA:PAI-1-i from the cell surface also requires uPAR binding to LRP. These results document functional interactions between scavenger receptors (LRP) and uPAR suggesting a role for LRP in the regulation of plasminogen activation in cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADB257719
Entities
People
- Marilyn Farquhar
- Ralf-peter Czekay
Organizations
- University of California, San Diego