Regulation of Breast Carcinoma Chemotaxis By the Integrin (Alpha)6 (BETA)4
Abstract
Breast carcinoma invasion is a complex process in which the normal balance of cellular adhesion, proteolysis and directed migration is altered leading to penetration of the basement membrane and underlying stroma a. An understanding of the mechanism of carcinoma cell invasion is critical to the diagnosis, control, and eventual treatment of late stage breast cancer. Work from our lab has shown that expression of the integrin (Alpha)6(BETA)4 in breast carcinoma cells enhances their invasiveness. This finding demonstrates that the integrin (Alpha)6(BETA)4 regulates signaling pathways important in tumor invasion and offers an excellent model for studying these pathways. My data show that integrin (Alpha)6(BETA)4 expression in breast carcinoma cells leads to an increase in chemotaxis toward fibroblast conditioned medium or lysophosphatidic acid (LPA). Additionally, this integrin (Alpha)6(BETA)4-dependent chemotaxis is accompanied by the formation of lamellipodia. Both lamellae formation and chemotactic migration are inhibited or gated' by cAMP. My results reveal that a critical function of (Alpha)6(BETA)4 is to suppress the intracellular cAMP concentration by increasing the activity of a rolipram-sensitive, cAMP-specific phosphodiesterase (PDE). Also, my results show that RhoA controls lamellipodial formation and is required for directed migration. I hypothesize that integrin (Alpha)6(BETA)4 amplifies signals required for lamellipodial formation thereby enhancing chemotaxis. The goal of this study is to understand how integrin (Alpha)6(BETA)4 enhances lamellipodial formation and chemotaxis in breast carcinoma cells by identifying the signaling pathways involved in these processes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA368334
Entities
People
- Kathleen L. O'connor
Organizations
- Beth Israel Deaconess Medical Center