Transendothelial migration in breast cancer metastasis: when does c-Myb step in?
|Year of publication||2014|
|MU Faculty or unit|
|Description||The process of metastasis requires multiple mutual interactions of tumor and stromal cells. Endothelial cells (ECs) encounter tumor cells in multiple steps of metastatic cascade: ECs are manipulated to form tumor vasculature, to provide permeable entry to secondary environment prior the arrival of metastatic cell, ECs participate in multiple tissue-specific adhesive interactions with tumor cells, and endothelium is eventually penetrated by tumor cells during intravasation/extravasation. Because of different structural features of blood vessels in different organs, the extravasation efficiency contributes to organ-specific pattern of metastatic spread. Our previous results show the organ-specific spread induced by the c-Myb transcription factor, the progenitor/stem cell regulator, in breast tumors. We described, that the Myb-overexpressing 4T1 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. We hypothesized that the selective disadvantage of these tumor cells in lung colonization might result from the deficiency in extravasation. We demonstrate here that capacity of transendothelial migration (TEM) of breast cancer cells in vitro is slightly reduced by overexpressed c-Myb. However, c-Myb does not affect the adhesion rate of breast carcinoma cells to EC monolayer. Analysis of publically available microarray data revealed that breast cancer cell lines capable of TEM (TEM+) express lower amounts of MYB mRNA than TEM- cell lines. We further investigated vascular permeability induced by soluble factors secreted from tumor cells by in vitro transwell assay, and visualized the events associated with cytoskeletal remodeling during TEM by fluorescence confocal microscopy. The altered tumor-EC interactions might participate in the c-Myb-induced site-selective spread of breast tumors.|