Abstract 5540: CCN5/WISP-2 prevents leptin-induced breast cancer cell growth and migration

In menopausal women, one of the important risk factors for breast cancer is obesity/adiposity. Despite multiple studies, the biological mechanism by which obesity influences the breast carcinogenic process is still unclear. It is evident from various studies that leptin, a 16 kDa protein hormone over produced in obese people, plays a critical role in neovascularization and tumorigenesis in breast and other organs. Present studies demonstrate that leptin is able to induce proliferation and migration of estrogen receptor positive MCF-7 and ZR-75-1 breast tumor cell lines in a dose-dependent fashion but these effects are minimal in ER-negative MDA-MB-231 cells. Additionally, these studies found that leptin suppresses the transcriptional activation of anti-invasive gene CCN5/WISP-2. Although the suppression of CCN5 has no impact on the constitutive proliferation of these cells, it is critical for leptin-induced proliferation and necessary for the induction of in vitro migration of these cells because the addition of CCN5 recombinant protein into the media markedly inhibits the leptin-induced proliferation and migration. Collectively, these in vitro studies suggest that CCN5 may serve as a gatekeeper for leptin dependent breast carcinogenesis. 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 5540. doi:10.1158/1538-7445.AM2011-5540