Abstract C57: Obesity induced leptin-tumor stroma crosstalk in breast cancer: A link to cancer health disparity

Breast cancer cells can change tumor stromal cells by promoting growth, angiogenesis, invasion, and metastasis. Obesity is a risk factor of breast cancer, which is characterized by high levels of leptin. African American women show the highest incidence of obesity, most aggressive breast cancer, and highest mortality rate. Adipocytes and breast cancer cells synthesize leptin, which is a survival, pro-angiogenic, and proliferation factor for cancer cells; and also could affect tumor stromal cells [i.e, endothelial (EC) and fibroblasts]. Activated stromal cells could further contribute to the production of a tumor supportive extracellular matrix; thus, creating an ideal environment for the growth of cancer cells. We previously reported that leptin induces the expression of oncogenic and angiogenic factors (i.e, Notch and VEGF/VEGFR-2) in cancer cells and also a VEGFR-Notch axis in EC. However, the mechanisms by which leptin affects fibroblasts to promote cancer progression are not completely understood. We hypothesize that leptin induces Notch expression and activity that increase fibroblast proliferation and activation. Fibroblast cells (mouse embryonic NIH/3T3 stem and human cells) were challenged with leptin (0.6, 1.2, 6.2 nM) and inhibitors of Notch (DAPT). Notch proteins and mRNA, and leptin receptor (Ob-R) expression and fibroblast activation markers were determined after treatments. Our findings show that leptin induces Notch expression, proliferation and activation of embryonic fibroblast stem cells. This data further sustains the notion that high levels of leptin found in obese patients could contribute to tumor stroma activation and cancer development. Novel therapies targeting leptin signaling could be a new strategy for breast cancer prevention and treatment, which could be more relevant for obese African American breast cancer patients. Citation Format: Viola D. Lanier, Joy Milner, Adriana Harbuzariu, Diane Bowen, Ruben Rene Gonzalez-Perez. Obesity induced leptin-tumor stroma crosstalk in breast cancer: A link to cancer health disparity. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C57.