Cancer as a Matter of Fat: The Crosstalk between Adipose Tissue and Tumors

Abstract

Obesity has been linked to the increased risk and aggressiveness of many types of carcinoma. A state of chronic inflammation in adipose tissue (AT), resulting in genotoxic stress, may contribute to carcinogenesis and cancer initiation. Evidence that AT plays a role in cancer aggressiveness is solid and mounting. During cancer progression, tumor cells engage in a metabolic symbiosis with adjacent AT. Mature adipocytes provide adipokines and lipids to cancer cells, while stromal and immune cells from AT infiltrate carcinomas and locally secrete paracrine factors within the tumor microenvironment. This review focuses on the crosstalk between AT and tumor cells that promotes tumor growth and increases cellular lipid metabolism, metastasis, and chemoresistance.

Figure 1 Key Figure

The roles of cells from adipose tissue in the successive steps of cancer progression Interaction between AT and epithelium during cancer initiation and progression. WAT secretes factors that promote transformation of benign epithelium, induce the EMT and the switch to increased fatty acid metabolism in cancer cells, and eventually promote metastases and chemoresistance. Both endocrine WAT factors and paracrine factors from WAT-derived cells (adipocytes, ASC, and leukocytes) infiltrating tumors contribute to the steps of cancer progression. Abbreviations: AT, adipose tissue; WAT, white adipose tissue; ASC, adipose stromal cells; BAT, beige adipose tissue; CAF, cancer associated fibroblasts; ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; FA, fatty acids; MMP, matrix metalloproteases; PD-1, Programmed Death-1; ROS, reactive oxygen species; TAM, tumor-associated macrophages