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

Kaenel, Philip; Antonijevic, Milica; Richter, Stefanie; Küchler, Samuel; Sutter, Nora; Wotzkow Alvarez, Carlos; Strange, Robert; Andres, Anne-Catherine (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(2), pp. 357-69. Athens: Spandidos Publications 10.3892/ijo.2011.1238

Full text not available from this repository.

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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital [discontinued] > Forschungsgruppe Biologie und Karzinogenese der Brustdrüse [discontinued]
UniBE Contributor:	Kaenel, Philip, Wotzkow Alvarez, Carlos, Andres, Anne Catherine
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1019-6439
Publisher:	Spandidos Publications
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:21
Last Modified:	05 Dec 2022 14:06
Publisher DOI:	10.3892/ijo.2011.1238
PubMed ID:	22020958
Web of Science ID:	000298824400003
URI:	https://boris.unibe.ch/id/eprint/7005 (FactScience: 212140)