Abstract
Abstract There is increasing evidence that many human cancers, including breast cancer, are driven and maintained by a cellular subcomponent that displays stem cell properties. These “cancer stem cells” (CSCs) may also mediate tumor metastasis and contribute to treatment resistance and relapse. Our laboratory has identified cellular markers and developed in vitro and mouse models to isolate and characterize normal and malignant human mammary stem cells. We have previously demonstrated that breast cancer cell lines contain subpopulations with stem cell properties that can be isolated by virtue of their expression of Aldehyde dehydrogenase (ALDH) as assessed by the Aldefluor assay. We demonstrated, among microRNAs differently expressed in Aldefluor-positive and Aldefluor-negative populations of breast cancer cell lines we identified micrRNA100 (mir100). We found that mir100 is significantly increased in Aldefluor-negative compared to Aldefluor-positive populations. Utilizing a tetracycline inducible lentivirus driving mir100 expression, we found that induction of mir100 expression decreased the ALDH-positive population of SUM159 cells in vitro as well as in mouse xenografts where this reduction was associated with decreased tumor growth. Furthermore, induction of mir100 expression immediately upon orthotopic implantation or intracardiac injection completely blocked subsequent tumor growth and metastasis formation. These studies demonstrate that mir100 plays a functional role in the self-renewal and differentiation of breast cancer stem cells. Furthermore, the TET-inducible mir100 system allows for controlled regulation of the cancer stem cell population providing a valuable model to simulate the effects of CSC-directed therapies on breast cancer growth and metastasis. 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 3330. doi:10.1158/1538-7445.AM2011-3330
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