Abstract A13: Lineage-specific roles for the Ron receptor in prostate cancer

Abstract

Prostate cancer is one of the leading causes of cancer-related death among men in the United States due, in part, to its aggressiveness and resistance to therapy following a remission period. Receptor tyrosine kinases are emerging as potential therapeutics in prostate cancer. One of these receptors, the Ron receptor tyrosine kinase, has been shown to be overexpressed in a variety of cancers where it modulates many cellular functions relevant to cancer such as invasion, inflammation, angiogenesis, and proliferation. Ron is expressed primarily on epithelial cells and macrophages, which are both important in regulating the prostate tumor microenvironment. Our laboratory has shown recently that crossing mice lacking the Ron receptor (Ron TK−/−) to TRAMP+ mice, which develop prostate adenocarcinomas by 30 weeks of age, leads to a significant decrease in prostate tumor mass, tumor vascularization, and proangiogenic chemokine secretion relative to TRAMP+ control mice. In addition, we have shown that loss of Ron in the myeloid lineage (monocytes and granulocytes) leads to decreases in prostate tumor establishment using an orthotopic model of prostate cancer. Given this, we therefore wished to understand what role the Ron receptor plays in specific cell types relevant to prostate cancer progression. By knocking out Ron in the prostate epithelium or myeloid lineage (monocytes, macrophages, and granulocytes) and crossing these mice onto a TRAMP background, we hope to investigate the effect of lineage-specific loss of Ron in mediating prostate cancer development and progression. We hypothesize that Ron receptor signaling in the prostate epithelium and in myeloid cells promotes prostate tumorigenesis via interdependent mechanisms. By understanding the interdependent mechanisms of Ron signaling in the prostate epithelium and myeloid lineage, our studies will identify a potential novel signaling pathway, its combined and cell-type specific role in regulating prostate tumorigenesis, and suggest novel avenues for the development of new therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A13.