Tumor genes regulated in obesity-mediated breast cancer
We developed a post-menopausal orthotopic ER+ breast cancer model that we used to investigate mechanisms of obesity mediated lung metastases. Obesity altered the immune cell composition and function in the primary tumor microenvironment. To identify tumor-derived genes associated with obesity mediated lung metastases we performed RNASeq on tumors grown in lean vs obese mice. From these results we identified a hepatocyte growth factor (HGF)-c-Met (HGF receptor)-CCL2 loop recruiting metastasis-promoting cells. Overall design: 6 weeks-old female C57BL/6 mice were ovariectomized. Two week later mice were fed with high fat diet (5.1 kcal/g, 60% calories from fat) or regular diet (3.6 kcal/g, 10% calories from fat) for 6 weeks. In average HFD fed mice gained a 35% increase in body weight. 10E6 Py230 cells were injected in the 4th mammary gland, and 4 tumors per conditions were harvested at day 56 after tumor initiation.