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'Normalizing' the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin

Abu-Tayeh, Hanan; Weidenfeld, Keren; Zhilin-Roth, Alisa; Schif-Zuck, Sagi; Thaler, Sonja; Cotarelo, Cristina; Tan, Tuan Z.; Thiery, Jean P.; Green, Jeffrey E.; Klorin, Geula; Sabo, Edmond; Sleeman, Jonathan P.; Tzukerman, Maty; Barkan, Dalit

Abstract:
Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-αvβ3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids’ reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAM$^{high}$CD49f$^{low}$CD24$^{+}$ and Int-αvβ3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-αvβ3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-αvβ3 were injected into a humanized mouse model, differentiated tumors devel ... mehr


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Jahr 2016
Sprache Englisch
Identifikator DOI: 10.1038/cddis.2016.387
ISSN: 2041-4889
URN: urn:nbn:de:swb:90-655906
KITopen ID: 1000065590
HGF-Programm 47.01.01; LK 01
Erschienen in Cell death & disease
Band 7
Heft 12
Seiten Art. Nr.: e2491
Lizenz CC BY 4.0: Creative Commons Namensnennung 4.0 International
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