Abstract A098: Contribution of macrophages to FGFR-dependent breast cancer

Abstract

Abstract Genomic profiling studies have demonstrated that a number of potentially targetable pathways are capable of contributing to breast cancer, including the fibroblast growth factor receptor (FGFR) pathway. Our studies focus on understanding the mechanisms through which FGFR1 activation in tumor cells leads to pro-tumorigenic changes in the microenvironment. Specifically, using an in an in vivo model of fibroblast growth factor receptor 1 (FGFR1)-induced mammary tumorigenesis, we have found that following FGFR1 activation in mammary epithelial cells, macrophages are recruited to the hyperplastic regions where they are required for angiogenesis and epithelial cell proliferation. To identify the factors that contribute to the pro-tumorigenic microenvironment, we have developed two- and three-dimensional co-culture in vitro models to mimic what is observed in vivo. Using these in vitro models, we have identified that soluble factors derived from FGFR1-activated epithelial cells lead to the upregulation of target genes in macrophages that promote tumor formation, invasion, and migration. Findings from the in vitro studies are further assessed using a mouse mammary tumor model utilizing orthotopic transplants into immunocompetent mice. These model systems will help us identify novel regulators of mammary tumorigenesis and provide new insight into the mechanisms by which macrophages promote tumor formation. Citation Format: Nicholas J. Brady, Mariya Farooqui, Laura Bohrer, Kaylee Schwertfeger. Contribution of macrophages to FGFR-dependent breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A098.