Abstract 5383: Metabolic profiling of compressed stromal cells in the breast peritumor

Breast cancer represents a significant public health concern for women across the globe. Although the breast peritumor is increasingly recognized for its active role in modulating breast tumor growth and progression, its biophysical relationship with the tumor is poorly understood. Of particular interest is the effect of compressive forces imparted onto the peritumor by the growing mammary tumor. In this study, we found that compression metabolically reprograms stromal cells—namely, fibroblasts and adipocytes—found in the breast peritumor in vitro. Using fluorescence lifetime imaging microscopy, we discovered that fibroblasts and differentiated adipocytes under compression adopt a more glycolytic state whereas compressed pre-adipocytes appear to favor oxidative phosphorylation. We were able to confirm this metabolic shift in fibroblasts using bulk RNA sequencing, with pathway analysis showing that compressed fibroblasts significantly downregulate oxidative phosphorylation and strongly enrich glycolysis. Moreover, by measuring glucose uptake, we found that compression moderately increases glucose uptake in fibroblasts. Furthermore, through single cell transcriptomic analysis of breast cancer patients, we discovered that, in relation to those found in normal (compression (-)) tissue, fibroblasts and mature adipocytes in the peritumor (compression (+)) tend to favor glycolysis. It remains to be determined, however, to what degree this metabolic reprogramming is a direct consequence of external tumor compression. Citation Format: Julian Najera, Hao Chen, Scott Howard, Meenal Datta. Metabolic profiling of compressed stromal cells in the breast peritumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5383.