TY - JOUR AB - Cancer most probably originates from stem/progenitor cells and exhibits a similar cell hierarchy as normal tissues. Moreover, there is growing evidence that only the stem cells are capable of metastasis formation. We have previously shown that overexpression of a dominant negative ephrin-B2 mutant interferes with mammary gland differentiation and confers a metastatic phenotype to NeuT-induced mammary tumors with an increase in cells with stem/progenitor characteristics. To investigate the role of ephrin-B2 in the control of the mammary stem cell niche, we analyzed the mammary stem and progenitor cell populations in transgenic mice overexpressing the mutant ephrin-B2. Quantification by FACS analysis revealed a significant increase of cells in the basal/alveolar cell-, the bi-potent progenitor- and the stem cell-enriched fractions. Moreover, the supposed precursors of estrogen receptor-positive cells were elevated in the stem cell-enriched fraction. In contrast, the epithelium from transgenic mice overexpressing the native ephrin-B2 gene showed an augmentation of the luminal cell- and the bi-potent progenitor-enriched fractions. Repopulation assays revealed that the epithelial cells of truncated ephrin-B2 transgenic epithelial cells have a higher regeneration capacity than those of controls and of native ephrin-B2 transgenic mice, confirming the augmentation of stem cells. Morphologically, these outgrowths exhibited impaired basal/luminal compartmentalization and epithelial polarization. These results demonstrate that deregulated ephrin-B2 expression interferes with the regulation of the stem cell niche and leads to a shift of the differentiation pathway and may thereby contribute to the acquisition of the metastatic phenotype long before carcinogenic growth becomes apparent. AD - Department of Clinical Research, University of Bern, Tiefenaustrasse 120c, CH-3004 Bern, Switzerland null Department of Clinical Research, Tiefenaustrasse 120c, CH-3004 Bern, Switzerland AU - Kaenel,Philip AU - Antonijevic,Milica AU - Richter,Stefanie AU - Küchler,Samuel AU - Sutter,Nora AU - Wotzkow,Carlos AU - Strange,Robert AU - Andres,Anne-Catherine DA - 2012/02/01 DO - 10.3892/ijo.2011.1238 EP - 369 IS - 2 JO - Int J Oncol KW - CD49f CD24 estrogen receptor mammary gland repopulation assay transgenic mice PY - 2012 SN - 1019-6439 1791-2423 SP - 357 ST - Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway T2 - International Journal of Oncology TI - Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway UR - https://doi.org/10.3892/ijo.2011.1238 VL - 40 ER -