A Genetic Model for the Breast Cancer Microenvironment
Final rept. 1 Sep 2007-31 Aug 2008
TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
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Despite improved treatments, metastatic breast cancer kills more than 40,000 women each year in the US. Little is known about what factors in the host contribute to the establishment of metastases. To understand how the host microenvironment affects the behavior of cancer cells, we have used the zebrafish, a powerful, genetically tractable vertebrate model system with cancer biology very similar to human. Our studies focus on the interaction of the chemokine receptor CXCR4b, expressed in breast cancer cells, with its ligand sdf-1, expressed in the microenvironment. This interaction is a key determinant of metastatic potential. We have selected breast cancer lines with varying expression levels of CXCR4b and sdf-1. We have selectively altered the expression of sdf-1 in zebrafish embryos using knockdown and targeted expression techniques. As proof-of-principle, we shown that perturbing embryo sdf-1 directly affects the migration of endogenous primordial germ cells, which also depend on CXCR4b. In subsequent work, we will assess the effect of these manipulations on survival and spread of breast cancer xenografts. The goal of this study is to understand how the host microenvironment influences the development of breast cancer metastasis.
- Anatomy and Physiology
- Medicine and Medical Research