Hypoxia promotes dissemination of multiple myeloma through acquisition of endothelial to mesenchymal transition-like features

The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the endothelial to mesenchymal transition (EMT) process. In this study, we hypothesized that MM associated hypoxic conditions activates EMT related proteins and promotes metastasis of MM cells. Hypoxia activated EMT-related machinery in MM cells, decreased expression of E-cadherin and consequently decreased adhesion of MM cells to the BM and enhanced egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, and consequently increased the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia in order to regulate tumor dissemination as a therapeutic strategy are warranted.