| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
|
| Zdroj: |
Cell death & disease, 7 (12), Art. Nr.: e2491 |
| ISSN: |
2041-4889 |
| DOI: |
10.5445/ir/1000065590 |
| Popis: |
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-��v��3), 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-��v��3 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-��v��3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-��v��3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-��v��3 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-��v��3 can potentially promote ���normalization��� of their malignant phenotype and may prevent the malignant cells from progressing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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