The Adipose Tissue at the Crosstalk Between EDCs and Cancer Development

Abstract

Obesity is a major public health concern at the origin of many pathologies, including cancers. Among them, the incidence of gastro-intestinal tract cancers is significantly increased, as well as the one of hormone-dependent cancers. The metabolic changes caused by overweight mainly with the development of adipose tissue (AT), insulin resistance and chronic inflammation induce hormonal and/or growth factor imbalances, which impact cell proliferation and differentiation. AT is now considered as the main internal source of endocrine disrupting chemicals (EDCs) representing a low level systemic chronic exposure. Some EDCs are non-metabolizable and can accumulate in AT for a long time. We are chronically exposed to low doses of EDCs able to interfere with the endocrine metabolism of the body. Importantly, several EDCs have been involved in the genesis of obesity affecting profoundly the physiology of AT. In parallel, EDCs have been implicated in the development of cancers, in particular hormone-dependent cancers (prostate, testis, breast, endometrium, thyroid). While it is now well established that AT secretes adipocytokines that promote tumor progression, it is less clear whether they can initiate cancer. Therefore, it is important to better understand the effects of EDCs, and to investigate the buffering effect of AT in the context of progression but also initiation of cancer cells using adequate models recommended to uncover and validate these mechanisms for humans. We will review and argument here the potential role of AT as a crosstalk between EDCs and hormone-dependent cancer development, and how to assess it.

Impact of Endocrine Disruptors upon Non-Genetic Inheritance

“…A recurrent exposure to low doses of EDCs may interfere with the endocrine metabolism. EDCs have been implicated in the development of cancers, mainly in hormone-dependent cancers such as prostate, testis, breast, endometrium or thyroid cancer [ 45 ]. It has been shown in a fish model that EDC-responsive genes are differentially methylated after exposure to EDCs.…”

Exposure to Low Doses of Oxybenzone During Perinatal Development Alters Mammary Gland Stroma in Female Mice

“…It has been suggested that unlike hyperplasia (an increase in the number of adipocytes), hypertrophy is a sign of dysfunctional development of the adipocyte cells. Moreover, expanded adipocytes can lead to cellular hypoxia and chronic sub-inflammation along with an increased influx of immune cells and local increase of reactive oxygen species ( Bokobza et al, 2021 ). Therefore, markers of inflammation, and possibly, the mechanisms by which inflammation in the mammary stroma affect the long-term health of the epithelium should be evaluated in future research studies.…”

Adiponectin: A player in the pathogenesis of hormone-dependent cancers

“…They are structurally highly related, as their protein sequence shares 67% identity, and include7 transmembrane domains, an extracellular carboxy-terminus and an intracellular amino-terminus, a structure that is opposite to that of all other G-coupled protein receptors. AdipoR1 and AdipoR2 are also highly conserved, since they share 95 and 97% identity between mice proteins, respectively (8)(9)(10).…”