The pleiotropic roles of adipocyte secretome in remodeling breast cancer

Breast cancer is the leading female cancer type and the cause of cancer-related mortality worldwide. Adipocytes possess important functions of energy supply, metabolic regulation, and cytokine release, and are also the matrix cell that supports mammary gland tissue. In breast cancer tumor microenvironment (TME), adipocytes are the prominent stromal cells and are implicated in inflammation, metastatic formation, metabolic remodeling, and cancer susceptibility.It is well-established that adipocyte secretome is a reservoir engaged in the regulation of tumor cell behavior by secreting a large number of cytokines (IL-6, IL-8, and chemokines), adipokines (leptin, adiponectin, autotaxin, and resistin), lipid metabolites (free fatty acids and β-hydroxybutyrate), and other exosome-encapsulated substances. These released factors influence the evolution and clinical outcome of breast cancer through complex mechanisms. The progression of breast cancer tumors revolves around the tumor-adipose stromal network, which may contribute to breast cancer aggressiveness by increasing the pro-malignant potential of TME and tumor cells themselves. Most importantly, the secretome alterations of adipocytes are regarded as distinctly important targets for breast cancer diagnosis, treatment, and drug resistance.Therefore, this review will provide a comprehensive description of the specific adipocyte secretome characteristics and interactions within TME cell populations, which will enable us to better tailor strategies for tumor stratification management and treatment.