From mouse to humans: detecting preventing vaccination targets associated to breast cancer stem cells

The efficacy of cancer treatments have improved constantly in the last decade. However, therapeutic resistance and the lack of curative treatments in metastatic disease, raises the question if conventional anticancer therapies target the right cells. Indeed, these treatments might miss cancer stem cells (CSCs), which might also represent a more chemoresistant and radioresistant subpopulation within cancer. In this view using vaccines in tertiary prevention of cancer, i.e. residual disease treatment, might be particularly effective if vaccine-elicited immune response is directed against CSC oncoantigens (OAs) proteins required for the neoplastic process the chance that the tumour will evade the vaccine should be reduced. An important task to devise effective CSC preventive vaccines is therefore the identification of CSC OAs. In this experiment we used a cell line (TuBo) derived by the mouse breast cancer model BALB-neuT and its CSC subpupolation, enriched by mean of mammosphere formation. Integrating data derived by gene and exon-level transcription profiling of the above experiments with public available normal and tumor datasets we identified two new breast cancer CSC OAs: TMPRSS4 and xCT. Both genes are linked to invasion, migration and metastasis. Furthermore, we observed that alternative splicing events discriminating TuBo cells, grown in adherent medium, with respect of TuBo mammospheres, produced growing in no-adherent medium, are very limited. We detect only one clear splcing event characterizing the beta-isoform of Rabgap1l gene.

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