Anti-Estrogen Regulation of Macrophage Products that Influence Breast Cancer Cell Proliferation and Susceptibility to Apoptosis
Abstract
We have characterized the regulation of gene expression in MCF-7 breast cancer cells and THP-l macrophages as a model of epithelial cell-stromal cell interaction in breast cancer progression. THP-1 macrophages enhanced the proliferation of MCF-7 cells, protected them against tamoxifen killing, and induced the expression of several MCF-7 angiogenesis-related genes, including IL-8 (interleukin-8), OPN (osteopontin), MDK (Midkine), TGFRl/2/3 (TGF receptors 1, 2, 3), and 1D3 (inhibitor of differentiation 3). Pre-treatment of THP-l macrophages with 1 mM aspirin abrogated their protection of MCF-7 cells against tamoxifen killing, while down-regulating several angiogenesis-related genes in the macrophages. Reciprocally, MCF-7 cells altered the expression of angiogenesis-related genes in the macrophages: THP-1 macrophages expressed both vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) genes when cultured alone; however, in the presence of MCF-7 cells, PEDF expression was dramatically down-regulated. Because PEDF is a potent inhibitor of angiogenesis, the ability of MCF-7 cells to suppress PEDF expression in tumor-associated macrophages, while sustaining VEGF expression, may be a mechanism by which tumor cells regulate macrophage function to promote tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA431834
Entities
People
- Theodore Bremner
Organizations
- Howard University