Role of Smooth Muscle Actin in Stromal-Epithelial Interactions
Abstract
The structure and homestasis of normal breast parenchyma is maintained by dynamic interactions between breast epithelial cells and their associated stroma. During breast carcinogenesis, these stromal-epithelial interactions are increasingly deregulated. Stromal fibroblasts in invasive breast carcinomas (i.e., carcinomas associated fibroblasts, CAF) differ from fibroblasts associated with normal breast. These differences include the production of increased amounts of type-specific collagens, the over expression of various growth factors, proteases and protease inhibitors, and acouisition of the myofibroblast phenotype, characterized by alpha-smooth muscle actin (SMA) expression. SMA functions to stop the migraton of breast fibroblasts and contributes to the contraction of myofibroblasts. These activities involve alterations in adhesion moleculares and cytoskeletal organization, which also affect expression of other molecules, such as extracellular matrix (ECM) proteins and proteases, by fibroblasts. In this project we test the hypothesis that expression of SMA is responsible for much of the CAF phenotype. RNA interference was utilized to inhibit expression of SMA in CAF. SMA-inhibited and SMA-expressing CAF were compared for the expression of a variety of cell adhesion mole%ules, ECM proteins, and ECM modulating proteases. We demonstrate that SMA in CAF affects the expression of several cell adhesion molecules, ECM proteins and ECM.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA421964
Entities
People
- Andra R. Frost
Organizations
- University of Alabama