Microenvironment-dependent function of c-Myb in breast cancer: the focus on the tumorendothelial cell interactions

Deregulation of the c-Myb transcription factor, the stem/ progenitor cell regulator, occurs frequently in breast cancer and other malignancies. The ambivalent function of c-Myb in breast tumors has been reported. We described that the MYB overexpression in breast carcinoma cell lines can differentially affect cell migration and invasion in vitro depending on chemotactic/chemokinetic conditions and matrix composition. The Myb-overexpressing mammary tumors in syngeneic BALB/c model rarely metastasized to lungs in contrast to control tumors, though the formation of the bone and liver metastases was not affected. The selective disadvantage of these cells in lung colonization might result from their inability to penetrate a vessel wall and underlying basement membrane in lung parenchyma. We therefore targeted the specific aspects of tumor-endothelial cell interactions and demonstrated that capacity of transendothelial migration of the MYB -overexpressing MDA-MB-231 cells was impaired. The differential regulation of cytoskeleton dynamics and suppression of interstitial collagenase may contribute to the damaged extravasation and site-selective metastases of the MYB -overepressing breast tumors.

This work was funded by grant grant NT 13441–4/2012 of the Internal Grant Agency of Ministry of Health of the Czech Republic, and by the European Regional Development Fund and the State Budget of the Czech Republic (RE CAMO, CZ.1.05/2.1.00/03.0101) via the human resources project “IntegRE CAMO: Intelectual Anchor” (CZ.1.07/2.3.00/20.0097).