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

Minh Ngoc Duong,Aline Geneste,Catherine Muller,Charles Dumontet,Xia Li,Frederique Fallone

doi:10.18632/oncotarget.18038

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.

Highlights

Adipose tissue (AT) is one of the main components of the human body
Co-culture of adipocytes with breast cancer cells led to adipocyte delipidation [31]. In line with these data, we showed that cancerassociated adipocytes (CAAs) located at the invasive front of breast cancer displayed smaller sizes and less lipid than adipocytes far from the tumors [31], an observation that has been largely confirmed by several groups in a wide range of solid tumors [25, 38, 132]
In opposition to the increase in fatty acid β-oxydation (FAO) observed at primary sites, a recent study proposed that the crosstalk between prostate tumor cells and bone marrow adipocytes led to decreased mitochondrial oxidative phosphorylation in tumor cells associated to increased expression of glycolytic enzymes and increased lactate production via oxygen-independent mechanism of HIF-1α activation [133]

Summary

Introduction

Adipose tissue (AT) is one of the main components of the human body. Imaging methods, including computed tomography, magnetic resonance imaging and ultrasound, have allowed the quantification of adipose tissue. Nieman et al showed that co-culture of human adipocytes with ovarian cancer cells promoted cancer cell growth both in vitro and in vivo [28]. Emerging studies suggest that the growth promoting-effect of adipocytes is observed at bone metastatic sites with an increase in bone tumor burden after intratibial injection of prostate cancer and melanoma cells in high fat diet-induced obese mice [39, 49].

Results

Conclusion