Identifying ECM Mediators of Tumor Cell Dormancy
Abstract
Characterize the compositional and functional changes in mammary stroma that result from tamoxifen treatment. Approach: R75 mature female Sprague Dawley rats were randomized into three groups of 25 each; Gp1 nulliparous control, and Gp 2 tamoxifen treated (0.5 mg/tamoxifen body weight, s.c. injection for 30 days)and Gp 3 tamoxifen treated (1.0 mg tamoxifen dose). ECM was harvested from the mammary glands of Gps 1 biochemical and functional characterizations. The ECM preparations have been subjected to LCMS and MALDI-TOF mass spec. Due to technical difficulties also developed two in vitro models to investigate the effects of tamoxifen on mammary stroma. ECM deposited by primary mammary fibroblasts isolated from tamoxifen treated rats, or primary control fibroblasts treated with tamoxifen in culture has been utilized for ECM proteomics method development. Conditions demonstrate fibronectin (FN) is downregulated by tamoxifen, in vitro and in vivo; observations consistent with data demonstrating that FN is up during MEC proliferation and down regulated at times of MEC loss; suggesting that loss of FN may be integral to a tumor suppressive microenvironment investigate functional changes in ECM, MDA-MB-231 cells were pre-mixed with control matrix or matrix isolated from tamoxifen treated rats and orthotinjected into nude mice. Tumor growth was reduced in mice injected with ECM isolated from tamoxifen treated rats, demonstrating that tamoxifen altered EC manner consistent with tumor cell dormancy. Finally, this work identifies ECM mediators of tumor cell dormancy and progression that can be targeted for drug development.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2007
- Accession Number
- ADA471107
Entities
People
- Pepper J Schedin
Organizations
- University of Colorado Health