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.

Figure 1. Obesity-associated circulating ASCs in breast cancer survivors

(A) Representative raw data from one non-obese (BMI < 30) and one obese (BMI > 30) participant. Viable MNC (mono nuclear cell) populations (upper right panel) were analyzed for CD34 intensity (lower right panel), and the gated CD34+ sub-population was further assessed for CD31 and CD45 (left panel). Abundance of CD34⁺/CD31⁻/CD45⁻ cells (% of total MNC) was numerated in each experiment. (B) Comparison of the abundance of circulating ASCs (CD34⁺/CD31⁻/CD45⁻) at baseline from the non-obese (n = 12) and obese (n = 12) breast cancer survivors. Mann-Whitney test was used to find the variability.

Figure 2. Enumeration of circulating ASCs before and after exercise

Thirteen obese breast cancer survivors who completed one of the three six-month exercise regimens were assessed for their circulating ASC readings before (pre-) and after the 6-month programs (post-). Mann-Whitney test was used to find the variability.