Homing mechanisms of myeloma cells.

A stricking feature of myeloma plasma cells concerns their tendency to reside in the bone marrow compartment during the main course of the disease evolution. This micro-environment provides the appropriate signals for growth and survival of the tumor cells. Since small amounts of myeloma cells are also detectable in the peripheral blood, it can be assumed that these cells represent lymph node and/or bone marrow derived tumor cells that directly contribute to disease spreading. The detection of such myeloma-related cells in the circulation implicates that they must be equipped with the appropriate surface molecules that mediate binding to endothelium, responsiveness to chemokines, transendothelial migration and extravasation. The specificity of this migration process might be a second important factor that determines the selective homing of myeloma cells in the marrow-microenvironment. During the end phase of the disease, increasing numbers of myeloma cells become detectable in the blood circulation and also extramedulary tumor localisation at other sites (liver, lung, ascites and pleural fluid) can occur. Molecular evolution towards stroma-independency in association with an enhanced extravasation potential are likely to be the key mechanisms that underlie this disturbed homing behaviour.