Adipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

Amino acid transporters are membrane transport proteins, most of which are members of the solute carrier families. Amino acids are essential for the survival of all types of cells, including tumor cells, which have an increased demand for nutrients to facilitate proliferation and cancer progression. Breast cancer is the most common malignancy in women worldwide and is still associated with high mortality rates, despite improved treatment strategies. Recent studies have demonstrated that the amino acid metabolic pathway is altered in breast cancer and that amino acid transporters affect tumor growth and progression. In breast cancer, glutamine is one of the key nutrients, and glutamine metabolism is closely related to the amino acid transporters. In this review, we focus on amino acid transporters and their roles in breast cancer. We also highlight the different subsets of upregulated amino acid transporters in breast cancer and discuss their potential applications as treatment targets, cancer imaging tracers, and drug delivery components. Glutamine metabolism as well as its regulation and therapeutic implication in breast cancer are also discussed.

Stromal immune cells constitute the tumor microenvironment. These immune cell subsets include myeloid cells, the so-called tumor-associated myeloid cells (TAMCs), which are of two types: tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Breast tumors, particularly those in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer and triple-negative breast cancer, are solid tumors containing immune cell stroma. TAMCs drive breast cancer progression via immune mediated, nonimmune-mediated, and metabolic interactions, thus serving as a potential therapeutic target for breast cancer. TAMC-associated breast cancer treatment approaches potentially involve the inhibition of TAM recruitment, modulation of TAM polarization/differentiation, reduction of TAM products, elimination of MDSCs, and reduction of MDSC products. Furthermore, TAMCs can enhance or restore immune responses during cancer immunotherapy. This review describes the role of TAMs and MDSCs in breast cancer and elucidates the clinical implications of TAMs and MDSCs as potential targets for breast cancer treatment.