Open Access

Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway

  • Authors:
    • Philip Kaenel
    • Milica Antonijevic
    • Stefanie Richter
    • Samuel Küchler
    • Nora Sutter
    • Carlos Wotzkow
    • Robert Strange
    • Anne-Catherine Andres
  • View Affiliations

  • Published online on: October 20, 2011     https://doi.org/10.3892/ijo.2011.1238
  • Pages: 357-369
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Abstract

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.

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February 2012
Volume 40 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Kaenel, P., Antonijevic, M., Richter, S., Küchler, S., Sutter, N., Wotzkow, C. ... Andres, A. (2012). Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway. International Journal of Oncology, 40, 357-369. https://doi.org/10.3892/ijo.2011.1238
MLA
Kaenel, P., Antonijevic, M., Richter, S., Küchler, S., Sutter, N., Wotzkow, C., Strange, R., Andres, A."Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway". International Journal of Oncology 40.2 (2012): 357-369.
Chicago
Kaenel, P., Antonijevic, M., Richter, S., Küchler, S., Sutter, N., Wotzkow, C., Strange, R., Andres, A."Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway". International Journal of Oncology 40, no. 2 (2012): 357-369. https://doi.org/10.3892/ijo.2011.1238