Abstract 6123: High-fat diets promote lung metastasis of breast cancer by activating lung fibroblasts

Abstract

Abstract Metastasis is the main cause of patient death among many tumor types including breast cancer and breast cancer patients with obesity have higher risk of distant metastases during 10-year follow-up. Diet is one of the main and manageable factors that cause obesity and regular intake of high-fat diets can induce obesity. In addition, fibroblasts, as the most abundant stromal cell type in tumor microenvironment, are involved in cancer metastasis. However, the role of fibroblasts and the downstream mechanism in metastasis of patients with high-fat diet remains unclear. In this study, we fed MMTV-PyMT transgenic mice with high-fat diet to obtain a high-fat tumorigenesis model, and isolate primary lung fibroblasts and then coculture them with breast cancer cells to explore the interaction. We found that a high-fat diet can significantly promote progression of primary breast cancer and lung metastasis, and that before weight difference shows, there is a different chemotactic influence of lung fibroblasts on breast cancer cell between high-fat diet and normal diet group. And we observed increased chemotactic function of primary lung fibroblasts in high-fat diet group. Moreover, tumor cells treated with primary lung fibroblasts in high-fat diet group show increased ability of adhesion, suggesting that high-fat diet chemoattracts breast cancer cell colonization by activating lung fibroblasts. Collectively, we explored the functional differences of lung fibroblast and the key factors for the lung colonization of recruited breast cancer cells. Our findings suggest that dietary patterns are associated with the risk of breast cancer metastasis and targeting activated fibroblasts in pre-metastatic microenvironment may serve as potential early therapeutic strategy to reduce breast cancer lung metastasis. Citation Format: Huiping Chen, Penghan Huang, Jianing Chen, Erwei Song. High-fat diets promote lung metastasis of breast cancer by activating lung fibroblasts [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 6123.