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. This lab's 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 vivo model of fibroblast growth factor receptor 1 (FGFR1)-induced mammary tumorigenesis, the researchers 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, they have developed two- and three-dimensional co-culture in vitro models to mimic what is observed in vivo. Using these in vitro models, they 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 identify novel regulators of mammary tumorigenesis and provide new insight into the mechanisms by which macrophages promote tumor formation.