Association of obesity and circulating adipose stromal cells among breast cancer survivors

Abstract

A positive association of obesity with breast cancer incidence and mortality is well established. Recent reports indicate that adipose stromal cells (ASCs) play an important role in breast cancer development and progression by producing estrogens and tumor-promoting cytokines. Furthermore, circulating ASCs have been uniquely detected in obese individuals, which is likely due to increased tissue remodeling and cell mobilization. The number of circulating ASCs is even more prominent in obese patients with colon and prostate cancers, both of which are exacerbated by obesity. To determine whether a similar association exists for breast cancer, we collected blood samples from a cohort of breast cancer survivors and enumerated circulating ASCs by flow cytometry on the basis of the previously established ASC-associated immunophenotype (CD34+/CD31−/CD45−). We found significantly higher levels of circulating ASCs (p < 0.001) in breast cancer survivors with body mass index (BMI) ≥ 30 kg/m2 than their non-obese counterparts (BMI < 30). We also compared circulating ASCs before and after exercise of only the obese subjects enrolled in a 6-month individualized exercise program, but found no statistically significant difference, likely due to limited number of subjects in the study. Our findings suggest that circulating ASCs can serve as a potential biomarker for future studies of the impacts of obesity and physical activity on breast cancer recurrence and survival.

Proteolytic Isoforms of SPARC Induce Adipose Stromal Cell Mobilization in Obesity

“…We have shown that ASC mobilized from WAT in obese mice are recruited by tumors and support their vascularization and growth . Consistent with that notion, our clinical studies have provided evidence that ASC are systemically mobilized in obesity . While a growing body of evidence indicates the role of ASC in mediating obesity pathophysiology, molecular mechanisms that govern ASC trafficking have remained obscure .…”

Signals from the Adipose Microenvironment and the Obesity–Cancer Link—A Systematic Review

“…ASC migrate to tumors in response to tumor production of CXCL1 and CXCL8 (34). The application of these pre-clinical findings to human disease was evidenced by data indicating that obese prostate cancer patients have increased tumor CXCL1 expression, circulating ASC, and tumor-infiltrating ASC (34) and has been further demonstrated by studies indicating an increase in circulating mesenchymal stromal cells (which include ASC) in obese disease-free donors (35) and colorectal cancer patients (36) as well as an increase in circulating ASC in obese breast cancer survivors (37). …”

An anti-inflammatory dietary intervention to reduce breast cancer recurrence risk: Study design and baseline data

“…ASCs were collected from the blood samples and analyzed as previously described [8]. Briefly, blood samples were centrifuged at room temperature for 25 min with no brake at 1600 × g .…”

“…Circulating Adipose Stromal Cells (ASCs) have been linked to cancer recurrence risk [6,7]. Our previous work has shown higher levels of ASCs in obese BCSs [8]. Furthermore, excess body fat has been shown to promote cancer in postmenopausal women by increasing levels of inflammation, insulin, and other hormones [9].…”