Metastasis accounts for most of cancer-related deaths. Paracrine signaling between tumor cells and the stroma induces changes in the tumor microenvironment required for metastasis. Transcription factor c-Myb was associated with breast cancer (BC) progression but its role in metastasis remains unclear. Here we show that increased c-Myb expression in BC cells inhibits spontaneous lung metastasis through impaired tumor cell extravasation. On contrary, BC cells with increased lung metastatic capacity exhibited low c-Myb levels. We identified a specific inflammatory signature, including Ccl2 chemokine, that was expressed in lung metastatic cells but was suppressed in tumor cells with higher c-Myb levels. Tumor cell-derived Ccl2 expression facilitated lung metastasis and rescued trans-endothelial migration of c-Myb overexpressing cells. Clinical data show that the identified inflammatory signature, together with a MYB expression, predicts lung metastasis relapse in BC patients. These results demonstrate that the c-Myb-regulated transcriptional program in BCs results in a blunted inflammatory response and consequently suppresses lung metastasis.
- MeSH
- apoptóza MeSH
- chemokin CCL2 genetika metabolismus MeSH
- lidé MeSH
- lokální recidiva nádoru genetika metabolismus patologie MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- myši MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové buňky kultivované MeSH
- nádorové mikroprostředí MeSH
- nádory plic genetika metabolismus sekundární MeSH
- nádory prsu genetika metabolismus patologie MeSH
- prognóza MeSH
- proliferace buněk MeSH
- protoonkogenní proteiny c-myb genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
