‘Normalizing’ the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1 December 2016
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| In: |
Cell death & disease
Year: 2016, Volume: 7, Issue: 12 |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2016.387 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/cddis.2016.387 Verlag, Volltext: http://www.nature.com/articles/cddis2016387 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 26.02.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/cddis.2016.387 |