Abstract 3327: Leptin receptors are expressed in breast cancer stem cells and leptin promotes their self-renewal and survival in mice

Abstract

Abstract Cancer stem cells (CSCs) are highly important in Breast cancer because they represent a subset of cancer cells that are generally undifferentiated, capable of self-renewal, resistant to therapy, and contribute to post-therapeutic tumor regrowth. CSCs can drive the malignant process and may generate the non-renewing differentiated cancer cells that comprise the bulk of the tumor. Here we show that in the Murine Mammary Tumor Virus (MMTV)-Wnt-1 transgenic mouse, a model of basal-like human breast tumors, leptin promotes tumorigenesis and the survival of breast CSCs. We show that leptin deficiency results in reduced outgrowth and burden of transplanted tumors. Second, leptin deficiency leads to depletion of cancer cells with a stem cell molecular signature. Third, the functional importance of the reduced cells is demonstrated by the fact that tumors from leptin-deficient mice led to reduced tumor outgrowth in vivo. Fourth, breast CSC enriched populations express the full-length leptin receptor. Finally, leptin promotes the viability of CSC enriched populations and increases tumorsphere generation in vitro. These results identify a critical role for leptin stimulation of breast CSCs and provide a strong suggestion that interfering with leptin signaling either via receptor blockade or a downstream pathway may provide therapeutic benefit. 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 3327. doi:10.1158/1538-7445.AM2011-3327