Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment
Menée sur des cellules de cancer du sein surexprimant CD10 et à l'aide de données issues d'essais cliniques, cette étude évalue l'association entre une signature basée sur l'expression de 12 gènes dans les cellules CD10+ du stroma et l'efficacité d'agents de chimiothérapie, en particulier pour les patientes atteintes d'un cancer du sein HER2+
Purpose: There is growing evidence that interaction between stromal and tumor cells is pivotal in breast cancer progression and response to therapy. Since the pioneer work of Allinen et al. suggested that during breast cancer progression striking changes occur in CD10+ stromal cells, we aimed to better characterize this cell population and its clinical relevance. Experimental design: We developed a CD10+ stroma gene expression signature (using HG U133 Plus 2.0) based on the comparison of CD10 cells isolated from tumoral (n=28) and normal (n=3) breast tissue. We further characterized the CD10+ cells by co-culture experiments of representative breast cancer cell lines with the different CD10+ stromal cell types (fibroblasts, myoepithelial and mesenchymal stem cells (MSC)). We then evaluated its clinical relevance in terms of in situ to invasive progression, invasive breast cancer prognosis and prediction of efficacy of chemotherapy using publicly available datasets. Results: This 12-gene CD10+ stroma signature includes among others genes involved in matrix remodeling (MMP11, MMP13, COL10A1) and genes related to osteoblast differentiation (periostin). The co-culture experiments demonstrated all three CD10+ cell types contribute to the CD10+ stroma signature, although MSCs have the highest CD10+ stroma signature score. Of interest, this signature demonstrated an important role in differentiating in situ from invasive breast cancer, in prognosis of the HER2+ subpopulation of breast cancer only, and potentially in non-response to chemotherapy for those patients. Conclusions: Our results highlight the importance of CD10+ cells in breast cancer prognosis and efficacy of chemotherapy, particularly within the HER2+ breast cancer disease.
Clinical Cancer Research , résumé, 2012