Obesity and melanoma: could fat be fueling malignancy?

Abstract

Summary Over the last decade, it has become increasingly clear that adipose tissue, and particularly adipocytes, contributes to tumor progression. Obesity, an ever‐increasing worldwide phenomenon, exacerbates this effect. The influence of obesity on melanoma remains poorly studied, although recent data do underline an association between the two diseases in both humans and murine models. Herein, we review the impact of obesity on melanoma incidence and progression and discuss the underlying mechanisms known to be involved. Adipose tissue favors the proliferation and aggressiveness of melanoma cells through a direct dialog, mediated by soluble factors and by exosomes, and through remodeling of the tumor microenvironment. This knowledge could, in the future, help to design new personalized therapeutic options for obese melanoma patients.

The potential role of leptin in tumor invasion and metastasis

“…It may be worth mentioning that melanoma is a highly aggressive form of skin cancer and the condition is frequently fatal if the tumor is not diagnosed early. An excess of adipose tissue may influence the development of melanoma and disease progression by different obesity-linked phenomena such as type 2 diabetes and enhanced release of leptin [158–161]. In an interesting study on melanoma, RNA was extracted from nodal tissue of 13 tumor-negative sentinel nodes, 10 tumor-positive sentinel nodes (micro-metastases<2 mm), and 11 tumor-negative non-sentinel nodes [162].…”

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

“…Obesity is a recognized factor to increase cancer incidence and progression (Gallagher & LeRoith, 2015). Studies in murine melanoma models and epidemiological data point to a positive correlation between obesity and melanoma incidence and progression (for a recent review, see Clement et al, 2017). Given their high propensity to invade adjacent tissues, including subcutaneous adipose tissue (AT), and to metastasize to distant organs, melanoma is the most aggressive cutaneous cancer.…”

“…Given their high propensity to invade adjacent tissues, including subcutaneous adipose tissue (AT), and to metastasize to distant organs, melanoma is the most aggressive cutaneous cancer. Studies in murine melanoma models and epidemiological data point to a positive correlation between obesity and melanoma incidence and progression (for a recent review, see Clement et al, 2017). Indeed, although controverted at first (Sergentanis et al, 2013), now, most epidemiological studies indicate that obesity increases the risk of developing melanoma, at least in men (Renehan et al, 2008;Dobbins et al, 2013).…”

Adipocyte vesicles: ‘all-in-one’ packages that stimulate tumor mitochondrial metabolism and dynamics

“…Given their high propensity to invade adjacent tissues, including subcutaneous adipose tissue (AT), and to metastasize to distant organs, melanoma is the most aggressive cutaneous cancer. Studies in murine melanoma models and epidemiological data indicate obesity is an established risk factor for melanoma incidence and progression [for a recent review, see (Clement et al, 2017)]. Adipocytes, the main component of the AT, reside in many cancer microenvironments and contribute to tumor progression through soluble factors, such as leptin or interleukin 6, and extracellular matrix remodeling (Andarawewa et al, 2005;Dirat et al, 2011;Duong et al, 2017).…”