The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance

Abstract

Growing evidence has raised the important roles of adipocytes as an active player in the tumor microenvironment. In many tumors adipocytes are in close contact with cancer cells. They secrete various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Moreover, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, has been established as a risk factor for cancer incidence and cancer-related mortality. In this review, we summarize the mechanisms of the adipocyte-cancer cell crosstalk in both obese and lean conditions as well as its impact on cancer cell growth, local invasion, metastatic spread and resistance to treatments. Better characterization of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and suggest efficient therapeutic opportunities.

Visceral adipose tissue volume and CT‐attenuation as prognostic factors in patients with head and neck cancer

“…Dysfunctional adipocyte can secrete pro‐inflammatory cytokines and chemokines, which leads to inflammatory and fibrotic changes of adipose tissue . This alteration of adipose tissue is known to promote cancer cell growth and progression . Furthermore, cancer cells can inversely affect adipocytes by dedifferentiating adipocytes into fibroblast‐like cells, which increase the secretion of pro‐inflammatory cytokines and induce tumor cells to acquire more aggressiveness .…”

“…25 This alteration of adipose tissue is known to promote cancer cell growth and progression. 1,25,26 Furthermore, cancer cells can inversely affect adipocytes by dedifferentiating adipocytes into fibroblastlike cells, which increase the secretion of pro-inflammatory cytokines and induce tumor cells to acquire more aggressiveness. 1,25 In a previous study on nonhuman primates, increased attenuation of adipose tissue on noncontrast CT images corresponded to the inflammatory and fibrotic changes in adipose tissue, suggesting that the CT-attenuation of adipose tissue can be used as an indicator of the qualitative changes of adipose tissue.…”

“…Recently, evidence demonstrated that adipose tissue can play a role as an endocrine organ, beyond merely as a simple storage organ of excessive energy, and can contribute to carcinogenesis and cancer progression . Body mass index (BMI), which can be simply calculated from weight and height, has been widely used to estimate the amount of adipose tissue and many previous studies demonstrated worse prognosis for patients with high BMI in various kinds of malignancies, including colorectal cancer, breast cancer, pancreatic cancer, and hepatocellular carcinoma .…”

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

“…Adipocytes, the main component of 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). Recent findings highlight a metabolic cooperation between adipocytes and tumor cells, which is proving to be a key process in their tumor-promoting effects (Nieman et al, 2011;Balaban et al, 2017;Wang et al, 2017;Zhang et al, 2018).…”

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

“…Lipid metabolism reprogramming can be intrinsic to tumors or in response to external stimuli from the tumor microenvironment (3,4). In particular, adipocytes, cells specialized in maintaining energy homeostasis through storing and releasing lipids, are emerging as key regulators of tumor lipid metabolism (5).…”