Concise Review: The Obesity Cancer Paradigm: Exploration of the Interactions and Crosstalk with Adipose Stem Cells

Abstract

With the recognition of obesity as a global health crisis, researchers have devoted greater effort to defining and understanding the pathophysiological molecular pathways regulating the biology of adipose tissue and obesity. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence and aggressiveness of colon, hematological, prostate, and postmenopausal breast cancer cancers. The increased morbidity and mortality of obesity-associated cancers has been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue. The increased amount of adipose tissue also results in higher numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to impact cancer progression directly through several mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma. Emerging evidence indicates that obesity induces alterations in the biologic properties of ASCs, subsequently leading to enhanced tumorigenesis and metastasis of cancer cells. This review will discuss the links between obesity and cancer tumor progression, including obesity-associated changes in adipose tissue, inflammation, adipokines and chemokines. Novel topics will include a discussion of the contribution of ASCs to this complex system with an emphasis on their role in the tumor stroma. The reciprocal and circular feedback loop between obesity and ASCs as well as the mechanisms by which ASCs from obese patients alter the biology of cancer cells and enhance tumorigenesis will be discussed.

Adipose-Derived Stems Cells and Their Role in Human Cancer Development, Growth, Progression, and Metastasis: A Systematic Review

“…This study demonstrated that there is a wide breadth of available literature on the relationship between ASCs and cancer development, including mounting evidence in the areas of ASCs' role in the growth, progression, and metastasis of various malignancies (82)(83)(84). It appears that ASCs potentially play a role in multiple processes affecting tumor microenvironment; however, few articles specifically address the influence of ASCs on tumor microenvironment.…”

Analysis of circulating adipokines in patients newly diagnosed with solid cancer: Associations with measures of adiposity and tumor characteristics

“…HGF, pg/ml Adiponectin, ng/ml Leptin, pg/ml cancer cell proliferation, motility and overall cancer progression (25). Previous studies revealed that circulating leptin levels positively correlate with adiposity (11,38).…”

“…Obesity is a global health problem associated with a variety of metabolic diseases (24) and, at present, obesity is an established risk factor for epithelial tumors (25)(26)(27). Obesity is characterized as an excess of adipose tissue and defined by a BMI ≥30 kg/m 2 according to the WHO criteria (7).…”

“…A waist-hip ratio of ≥0.90 cm in males and ≥0.85 cm in females is also associated with an increased risk of metabolic complications (20). Previous epidemiological and clinical data revealed that obesity is associated with increased rates of colorectal, breast, renal and endometrial cancer, as well as several other types of solid malignancy (24,25). In addition, numerous studies have reported an association between visceral obesity and an increased risk of solid cancer and mortality (30)(31)(32)(33).…”

“…Adipokines refer to substances secreted from adipose tissue (10,11,17,35) and the obese state alters the physiological functions of adipose tissue, leading to differing adipokine secretion and influencing the levels and functions of a variety of adipokines (25,35). Adiponectin and leptin are abundant adipokines secreted by adipose tissue (10,11,17,26).…”