Project description:The Wnt/beta-catenin signalling pathway plays a central role in mammary stem cell homeostasis and in breast cancer. We employed the CD29hiCD24+ cell surface antigens to identify a subpopulation of mammary CSCs from Apc1572T/+, a mouse model for metaplastic breast adenocarcinoma, a subtype of triple-negative breast cancer in man. The MaCSCs are capable of recapitulating tumorigenesis when transplanted at low multiplicities in vivo, and of forming self-renewing organoids in vitro. Expression profiling of the different subpopulations sorted from normal and neoplastic mammary tissues revealed that the normal stem cell compartment is more similar to tumor cells than to their own differentiated progenies. Accordingly, Wnt signaling was found to be activated in the subpopulation encompassing normal mammary stem cells, though to a lesser degree than in the tumor cells. By comparing normal with cancer mouse mammary compartments, we were able to derive a MaCSC-specific signature composed of human orthologous genes able to predict poor survival, relapse and distant metastasis in human breast cancer. Finally, upon intravenous injection, only MaCSCs among the different tumor cell subpopulations are able to form metastatic lesions in a broad spectrum of anatomical sites. Overall, our data indicate that constitutive Wnt signaling activation interferes with mammary stem cell homeostasis leading to metaplasia and basal-like adenocarcinomas. The objective was to compare the: i) expression profiles between normal adult mammary stem cells and tumor cancer stem cells identified by Lin-CD29hiCD24+; ii) expression profile between adult stem cells and their differentiated counterparts both in normal and in tumor tissue to generate a cancer stem cell signature that can be used to compare with mammary human tumor expression data to predict survival and prognosis. To this aim five independent mammary adenocarcinomas from C57BL6/J Apc+/1572T mice and three independently isolated pools of mammary glands from C57BL6/J Apc+/+ mice were employed to sort 10,000 cells of each of the following populations: Lin-, Lin-CD29+CD24+ and Lin-CD29hiCD24+.

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Mammary tumors from K14-cre; ApcCKO/+ mice vs control mammary glands

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