Obesity and Cancer Metastasis: Molecular and Translational Perspectives

SIMPLE SUMMARY: A major challenge in treating cancer is when the cancer spreads from its original site to other parts of the body, a process also known as metastasis. In order to survive, the cancer cells must communicate with their environment for survival. It is increasingly recognized that fat tissue supports the survival of metastatic cancer cells allowing tumors to form at distant sites. Obese patients therefore have a worse prognosis due to accelerated tumor spread. Preventing cancer cells from communicating with fat tissue could therefore lead to new treatments aimed at stopping this spread. In this review we discuss how dysfunctional fat tissue supports the metastatic process and evaluate new therapies and lifestyle interventions that aim to prevent the communication between cancer cells and fat tissue. ABSTRACT: Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity–metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor–adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.