Abstract PO1-25-07: Obesity, breast cancer, and adipose-derived mesenchymal stem/stromal cells: The complex cross-signaling in the tumor microenvironment

Abstract

Abstract Objective: Breast cancer is the most frequently diagnosed cancer and a common cause of cancer related death in women. The breast cancer microenvironment (TME) is mainly composed of adipose tissue, consisting of adipocytes, adipose-derived mesenchymal stem/stromal cells (bASCs) and immune cells. Interestingly, it is well recognized that obesity, as indicated by increased body mass index (BMI≥30), is associated with an enhanced risk of more aggressive breast cancer (BC) as well as reduced patient survival. Therefore, we asked how BC affects the biological functionality of bASC, how obesity fuels this process, and on the other hand how these cells influence BC cells. Methods: Multiple molecular biological approaches as transcriptomic profiling and diverse functional assays were conducted to characterize at least 5 lean and obese patients derived bASCs samples near the TME (lean/obese-aT) or distant (lean/obese-dT). Afterwards, these cells were used to investigate the interaction with BC cells in 2-dimensional and 3-dimensional cell culture experiments. Moreover, immunohistological analyses were conducted in 16 lean and 16 obese breast cancer patients (grade 3-4). Results: The TME shifts bASCs towards cancer supporting phenotypes into an inflammatory cancer-associated phenotype, whereas ob-aT bASCs are prone to be cancer-educated into a myofibroblastic phenotype with a significant deregulated gene expression, cytokine/chemokine secretion, and reduced differentiation capacity. In corroberation, these BMI dependent de-differentiation processes could be confirmed in breast cancer tissue. Moreover, the cell-cell interaction of BC cells with aT-bASCs increased their proliferation, motility, and chemoresistance. Conclusions: The study found multiple pathways deregulated in bASCs associated with tumor promoting effects. Additionally, it revealed the role of aT-bASCs in promoting breast cancer progression on a functional and molecular level. Citation Format: Andreas Ritter, Christine Solbach, Juping Yuan. Obesity, breast cancer, and adipose-derived mesenchymal stem/stromal cells: The complex cross-signaling in the tumor microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-07.