Abstract 511: Adipocyte-derived fibroblasts contribute to the desmoplastic reaction in breast cancer: A new link between breast cancer and obesity

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Now, it is widely established that malignant tumors, not merely grow into a preexisting interstitial tissue, but they actively form a new stroma and modify their composition. Accordingly, one of the features of many carcinomas, particularly breast, is the presence of a dense collagenous stroma, the so-called desmoplastic response, comprising fibroblast-like cells which play a crucial role in tumor progression. Peritumoral fibroblasts are composed of several subpopulations that are morphologically undistinguishable and their origins remain debated. Our results suggest that a part of this fibroblast could arise from the “reorientation” of mature adipocytes, highly represented in breast tumour microenvironment. Using an original 2D coculture system, we show that mature adipocytes cocultivated with breast tumour cells for 3 to 8 days lose their lipid content as well as their adipocyte differentiation markers (HSL, Adipsin, Adiponectin, C/EBPα, PPARγ, Resistin). This process is associated with intense morphological and functional changes leading to an activated fibroblast phenotype (exhibition of actin stress fibers, increase of focal adhesion sites). In this way, we have identified for the first time a new fibroblastic population called Adipocyte Derived Fibroblast (ADF). Interestingly, the reorientation occur in vivo since the injection of far red fluorescent tumour cells into a mice fatpad containing GFP-expressing adipocytes induce the apparition of GFP-fibroblast-like cells that interdigitate with tumour cells. Moreover, our results show that the ADF phenotype depends on the reactivation of the Wnt/β-catenin pathway. Finally, ADFs exhibit an increase of migratory and invasive abilities, with enhanced profibrotic secretions (fibronectin and collagen 1) suggesting that these cells could be key players in desmoplastic reaction. Ongoing experiments are performed to assess the presence of ADFs in breast human tumors. Our results might provide an explanation for the poor prognosis observed in localized breast cancer in obese women, since the nature of the desmoplastic reaction and the secretion pattern of ADF might be profoundly altered in this physiopathogical condition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 511. doi:10.1158/1538-7445.AM2011-511