Abstract 3200: Examining the role of obesity and leptin signaling in triple negative breast cancer

Abstract Individuals with a high body mass index (BMI) have an increased risk of developing many adult cancers, including breast cancer. In triple negative breast cancer (TNBC), a clinically aggressive subtype of breast cancer, increased BMI is associated with more aggressive tumor types and a higher risk of recurrence. The differences in outcomes between obese and non-obese breast cancer patients is a consequence of the complex interplay between social, environmental, and physiological factors that contribute to the etiology of breast cancer. Therefore, understanding the complex signaling events in the obese tumor microenvironment is essential. Adipose stem cells (ASCs) are a component of the breast microenvironment, and are a subset of mesenchymal stem cells. ASCs from obese patients (obASCs) secrete higher levels various cytokines and adipokines that induce a more invasive phenotype in triple negative breast cancer cells compared to ASCs from lean individuals. Leptin, an adipokine that is expressed proportionally to fat mass, has been implicated in many cancers. Increased leptin and leptin receptor expression is associated with worse prognosis. This study seeks to examine the role of leptin signaling in triple negative breast cancer. Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model, a high fat diet was used to induce obesity in vivo. Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to a small peptide antagonist of the leptin receptor decreased the percentage of cells with CSC markers. PDX tumors implanted into diet-induced obesity mice had an increased volume compared to tumors implanted into lean controls. Conclusions: These molecular differences may contribute to the differences in cancer outcomes between obese and lean individuals with breast cancer, and further study of the crosstalk between obASCs and TNBC is critical. Citation Format: Courtney Brock, Maryl Wright, Khoa Nguyen, Katherine Hebert, Madlin Alzoubi, Thomas Cheng, Bridgette Collins-Burow, Matthew Burow. Examining the role of obesity and leptin signaling in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3200.