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.

1st Department of Pathological Anatomy St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Danylo Galytsky Lviv National Medical University Department of Oncology and Medical Radiology Lviv Ukraine

Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic

Department of Physiology and Department of Pathological Physiology Faculty of Medicine Masaryk University Brno Czech Republic

Institute of Biophysics of the Czech Academy of Sciences Brno Czech Republic

Institute of Physiology University of Zurich and Zurich Center for Integrative Human Physiology Zurich Switzerland

International Clinical Research Center Center for Biological and Cellular Engineering St Anne's University Hospital Brno Czech Republic

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