Interacting Inflammatory and Growth Factor Signals Underlie the Obesity-Cancer Link

Abstract

The prevalence of obesity, an established risk factor for many chronic diseases (including diabetes, cardiovascular disease, stroke, and several types of cancer), has risen steadily for the past several decades in the United States and many parts of the world. Today, ∼70% of U.S. adults and 30% of children are at an unhealthy weight. The evidence on key biologic mechanisms underlying the obesity-cancer link, with an emphasis on local and systemic inflammatory processes and their crosstalk with energy-sensing growth factor signaling pathways, will be discussed. Understanding the influence and underlying mechanisms of obesity on chronic inflammation and cancer will identify promising mechanistic targets and strategies for disrupting the obesity-cancer link and provide important lessons regarding the associations between obesity, inflammation, and other chronic diseases.

Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer

“…Obesity-associated dysfunctional adipose tissue is the "source" of proinflammatory factors, excessive sex steroids and adipokines, which makes adipose tissue a fundamental factor driving the obesity-breast cancer link. The possible mechanisms and factors contributing to the associations between obesity and breast cancer have been reported in previous studies: dysregulation of growth signals, inflammation, bioavailability of sex steroid hormones, microenvironment and metabolic changes in the obese state can all enhance cancer risk and progression (reviewed in (6,7)). …”

Dietary lipids and adipocytes: potential therapeutic targets in cancers

“…Another study showed that IL-6 in periprostatic adipose tissue conditioned medium was approximately 375 times greater than that in patient-matched serum, suggesting that periprostatic adipose tissue may have a role in modulating prostate cancer aggressiveness by serving as a source of IL-6 [115]. The roles of adipose tissue immunity on cancer growth have been discussed in reviews [116,117]. Interestingly, secretion of TNFα and IL-6 contributes to insulin resistance [18] which may subsequently drive the cancer growth when the circulating insulin level is further increased.…”

Body fatness, related biomarkers and cancer risk: an epidemiological perspective

“…The production of pro-inflammatory cytokines (e.g., tumor necrosis factor-alpha, interleukin-6) is triggered by adipose tissue and stimulates the hepatic secretion of acute phase proteins, such as C-reactive protein (CRP) [51] . Thus, greater body fatness is associated with low-grade inflammation both locally, i.e., in adipose tissue, and systemically (reflected by elevated plasma concentrations of inflammatory markers) [85] . Higher circulating inflammatory cytokines have been observed when comparing obese with non-obese individuals [86,87] .…”