Poster Topical Area: Diet and Cancer
Poster Board Number: 185
Obesity is a major risk factor for susceptibility to certain cancers, including colon, breast, and prostate. Hypertrophic adipose tissue is associated with increased adipose stem cell (ASC) number. Since ASC are recruited to tumor sites, further fueling tumorigenesis and the metastatic process, individual differences in ASC-mediated responses to biological stimuli such as an inflammatory milieu may contribute to an individual's disease susceptibility. This remains unclear. The objective of this work was to examine inter-individual differences in growth, gene expression and response to inflammatory stimuli in ASC from different donors.
Human ASC (one male and one female donor) were purchased from Lonza (Walkersville, MD). Cell proliferation was determined by sulforhodamine B assay. Gene expression markers for proliferation, steroid hormones, xenobiotic and immune pathways were determined using RT-PCR. After ASC treatment with or without lipopolysaccharide (LPS) for 2,4,6 and 8 hours, and interleukin-6 (IL-6), IL-8, IL-1β, monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α) expression were analyzed with RT-PCR. LPS-induced cytokine levels in media from the time course experiments were measured using the Bio-Plex cytokine assay kit.
Female ASC had 2-fold higher aryl hydrocarbon receptor (AHR) expression but ASC of both sexes had negligible expression levels of androgen receptor (AR) and estrogen receptor (ERα/β). Female ASC also had 2-fold higher proliferation rate than the male. Consistently, KI67, a proliferation marker, in female ASC, was 6-fold higher. Female ASC were more responsive to LPS, and exhibited a significantly greater fold induction of TNF-α, MCP-1 than the male ASC. Secretory protein levels of inflammatory cytokines, such as TNF-α, was significantly higher in the female ASC, while IL-6 secretion was higher in the male ASC.
Our findings suggest that inter-individual variability and/or possible sex differences in ASC may serve as a key determinant to obesity-associated cancer risks. Further validation of ASC-cancer risk at population level may lead the way for personalized treatment plans or diets as approaches to mitigate the development and/or progression of cancer.
Beltsville Human Nutrition Research Center, ARS,USDA