Abstract P6-01-02: Adipose tissue from breast cancer patients with the metabolic syndrome promotes proliferation and invasion of tumor cells and influences expression of genes involved in carcinogenesis.
Authors: McGarrigle SA , Carroll PA , Healy LA , Boyle T , Pidgeon GP , Kennedy MJ , Connolly EM 
Published: August 2014

Abstract
Background: Obesity is a public health issue of global proportions and is recognised as a risk factor for post-menopausal breast cancer. Similarly, the metabolic syndrome (MetS) is recognised as a high risk state for cancer in general. Previously we have shown that the MetS is common in postmenopausal breast cancer patients and is associated with a more aggressive tumor biology. However, the molecular mechanisms by which obesity and/or the MetS promote breast cancer remain unclear. Adipose tissue, including mammary fat, is a functionally active endocrine organ. The aims of this study were to determine whether factors secreted by mammary adipose tissue could affect tumor cell biology and to assess the effect of the MetS on this adipose depot and its subsequent effect on tumor cells.
Methods: Adipose tissue from fresh mastectomy specimens was cultured in serum free media for 72 h to produce adipose conditioned media (ACM). MCF-7 and MDA-MB 231 cell lines were treated with ACM for 24–48 h. Tumor cell function was then assessed by measuring cell proliferation (BrDU assay) and cell invasion. In addition, expression of 84 genes implicated in pathways involved in carcinogenesis was examined in these cell lines following ACM treatment, using quantitative PCR arrays.
Results: In the estrogen receptor (ER) positive MCF-7 cell line, ACM from MetS breast cancer patients promoted significantly greater proliferation compared to ACM from normal weight patients (203.6 ± 34.23 vs 136.8 ± 11.58%, p = 0.022). Similarly, ACM from MetS patients significantly increased invasion of MCF-7 cells compared to ACM from normal weight patients (153.4 ± 6.027 vs 126.3 ± 6.03% RFU, p = 0.006). No differences in cell proliferation or invasion between cells treated with ACM from MetS patients compared to ACM from normal weight patients were found in the ER negative MDA-MB-231 cell line. Treatment of MCF-7 cells with ACM from MetS patients resulted in significant alterations (&gt;2 fold up/down regulation) in expression of 11 genes involved in carcinogenesis. Primarily, genes implicated in invasion/metastasis and adhesion were differentially expressed between ACM-treated cells and cells treated with control media. On the other hand, when MDA-MB-231 cells were treated with ACM from the same patients only one gene, SERPIN B5 was significantly up-regulated &gt; 2 fold.
Conclusions: These data demonstrate that factors secreted from mammary adipose tissue from metabolically unhealthy patients promote proliferation and invasion of ER positive tumor cells and influence expression of genes involved in carcinogenesis in these cells. These effects were not observed in ER negative tumor cells suggesting that they may be mediated, at least in part by the estrogen receptor. These results have provided insight into how mammary adipose tissue may act via a paracrine mechanism to influence aspects of carcinogenesis and into how the metabolic syndrome may modulate this.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-01-02.