Mammary adipose tissue and cancer cell growth: The role of adipose tissue in the tumor microenvironment
e22009 Background: Worldwide, the prevalence of obesity is rapidly increasing, correlating with a direct increase in cancer rates1. Adipose tissue is considered an important endocrine organ producing several important hormones and cytokines including leptin and adiponectin. Mechanisms for the role of obesity in cancer states includes the excess or unregulated secretion of adipocytokines from adipose tissue, and potentially the metabolic syndrome (a cluster of co-morbidities linked to metabolic dysregulation). Mammary adipose tissue is proposed to play a vital role in the microenvironment of normal and tumour states within the breast2. Breast adipose tissue is a good candidate to investigate effects of obesity and metabolic disturbances on cancer states. Methods: Peritumoural (PT) adipose tissue adjacent to the tumour and distal adipose tissue (D) within the breast was sampled in 10 patients. The tissue was processed and cultured for 72hrs in serum free minimal cytokine media. A-MB-231 and MCF-7 breast cancer cell lines were then cultured with this adipocyte conditioned media (ACM) and cell proliferation response was then measured using BrDU assays. The adipocytokine profile at the mRNA and protein level was measured in ACM and adipose tissue for comparative differences using RT-PCR, ELISA and Cytokine Profiler technology. Results: ACM from both sites promoted tumour cell survival. There was however, a differential cell proliferation response noted between the peritumoural (PT) ACM and that from the distant (D) ACM. Pro-inflammatory mediators (VEGF, TNF-α, EGF) were also demonstrated a trend to be differentially expressed between the 2 sites. Conclusions: Proliferation of breast cancer cell lines occurs in response to ACM, with differential effects seen between peritumoural ACM and distant ACM. This may be mediated through increased pro-inflammatory or pro- mitogenic adipocytokine production in adipose tissue surrounding tumour. Further analysis will determine what role obesity and the metabolic syndrome plays in the results noted. No significant financial relationships to disclose.