Relationship Between Scavenger Receptors and uPA:PAI-1 and uPA Receptors in Breast Cancer
Abstract
The overall goal of this research is to gather detailed information about the cellular distribution and activities of components of the uPA-system in relation to scavenger receptors and RAP in normal and breast cancer cells. We have especially noted a number of differences between the cell lines in either expression levels of these proteins or their localization during the first year of our funding. Scavenger receptors show higher expression levels in estrogen-insensitive compared to estrogen-sensitive and normal cells, whereas newly obtained results for localization of uPAR show that this receptor unlike other GPI-linked proteins was not found in caveolae. Immunocytochemical and immunochemical studies provided evidence that at least one scavenger receptor, LRP, is colocalized with uPAR at the cell surface in several cell types and that both receptors can be coprecipitated. We also obtained evidence that uPAR and uPA are taken up into the cell by endocytosis via clathrin-coated vesicles. We have documented several abnormalities in the very aggressive estrogen-insensitive breast cancer cell line MDA-MB-231--i.e., they have a defect in recycling of LRP and they express a truncated form of uPAR incapable of binding uPA. The absence of the binding site for uPA may have significant impact in uPA cell surface activities and clearance in these cell and might contribute to the cancerous phenotype of these cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADB241037
Entities
People
- Marilyn Farquhar
- Ralf-peter Czekay
Organizations
- University of California, San Diego