Abstract
Abstract Obesity, a disease linked to increased number of adipocytes in various tissues, is now recognized as a risk factor for the development of breast cancer. Importantly, obesity has been reported to be associated with the occurrence of larger, more advanced tumors and aggressive cancer pathological features, including lymph node metastasis, advanced tumor stage, and high grade. Cancer-associated adipocytes (CAAs), the most abundant cellular component of breast cancer-associated stroma, promote carcinogenesis through paracrine effects. However, the molecular basis of adipocytes implication in breast carcinogenesis remains elusive. To shed light on this important phenomenon, we established and characterized normal adipocytes from post-plastic surgery of breast tissues. We have shown that these cells express various adipocyte biomarkers, including Leptin, TNF-α and FABP4. Furthermore, we investigated the role of the tumor suppressor p16 INK4A protein in adipocytes activation. We have found that specific down-regulation of p16INK4A by shRNA increased the expression/secretion levels of various adipokines including leptin, activated breast adipocyte and enhanced their migration/invasion abilities. Consequently, media conditioned with these cells stimulated the proliferation and the migration/invasion of breast cancer cells and enhanced endothelial cell differentiation into capillary-like structures. In addition, we have also shown that media conditioned with breast cancer cells decrease the expression of p16INK4A and increase the expression of leptin in adipocytes. These results provide the first indication that p16INK4A down-regulation in breast stromal adipocytes is an important step toward their activation. Citation Format: Huda H. Alkhalaf, Abdelilah Aboussekhra. p16INK4A down-regulation activates breast stromal adipocytes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 512. doi:10.1158/1538-7445.AM2013-512
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