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

• Verfasst von: Abu-Tayeh, Hanan [VerfasserIn]
• Verfasst von: Thaler, Sonja [VerfasserIn]
• Verfasst von: Sleeman, Jonathan P. [VerfasserIn]
• Titel: ‘Normalizing’ the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin
• Verf.angabe: Hanan Abu-Tayeh, Keren Weidenfeld, Alisa Zhilin-Roth, Sagi Schif-Zuck, Sonja Thaler, Cristina Cotarelo, Tuan Z. Tan, Jean P. Thiery, Jeffrey E. Green, Geula Klorin, Edmond Sabo, Jonathan P. Sleeman, Maty Tzukerman and Dalit Barkan
• E-Jahr: 2016
• Jahr: 1 December 2016
• Umfang: 15 S.
• Fussnoten: Gesehen am 26.02.2019
• Titel Quelle: Enthalten in: Cell death & disease
• Ort Quelle: London [u.a.] : Nature Publishing Group, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016,12) Artikel-Nummer e2491, 15 Seiten
• ISSN Quelle: 2041-4889
• DOI: doi:10.1038/cddis.2016.387
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1588139530

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 EpCAMhighCD49flowCD24+ 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 developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-αvβ3 can potentially promote ‘normalization’ of their malignant phenotype and may prevent the malignant cells from progressing.