Breast cancer fibroblasts and cross-talk

Abstract

The breast tumor microenvironment is one of the crucial elements supporting breast cancer tumor progression and metastasis. The fibroblasts are the chief cellular component of the stromal microenvironment and are pathologically activated and differentiated into breast cancer-associated fibroblasts (CAFs). The catabolic phenotype of breast CAFs arises due to metabolic reprogramming of these fibroblasts under pseudo-hypoxic conditions. The metabolic intermediates and ATP produced by the breast CAFs are exploited by the neighboring cancer cells for energy generation. The growth factors, cytokines, and chemokines secreted by the CAFs help fuel tumor growth, invasion, and dissemination. Moreover, the interplay between breast CAFs and cancer cells, mediated by the growth factors, ROS, metabolic intermediates, exosomes, and catabolite transporters, aids in building a favorable microenvironment that promotes cancer cell proliferation, tumor progression, and metastasis. Therefore, identifying effective means to target the reprogrammed metabolism of the breast CAFs and the cross-communication between CAFs and cancer cells serve as promising strategies to develop anti-cancer therapeutics. Henceforth, the scope of the present review ranges from discussing the underlying characteristics of breast CAFs, mechanisms of metabolic reprogramming in breast CAFs, and the nature of interactions between breast CAFs and cancer cells to studying the intricacies of reprogrammed metabolism targeted cancer therapy.

Keywords: Cancer-associated fibroblasts; Exosomes; Extracellular matrix; G-protein estrogen receptor; Metabolism; Warburg effect.