Cell Trafficking in Multiple Myeloma

Multiple myeloma (MM) is an incurable cancer of terminally differentiated plasma cells (PC) and represents the second most frequent hematologic malignancy in the western world. MM cells localize preferentially to the bone marrow where they interact closely with bone marrow stroma cells (BMSC) and extracellular matrix (ECM) proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advantage for MM cells and has a crucial role in mediating drug resistance to chemotherapy agents. As the name suggests, hallmark characteristic of MM is the ability to localize in multiple, distant bone sites causing disruption of the normal bone architecture and impairment of normal hematopoiesis. The pathogenic mechanisms of MM rely then not only on proliferation of cancerous cells, but also on the ability of myeloma cells to traffic between sites and home to appropriate survival niches. Identifying the mechanisms that regulate the homing of MM cells to the bone marrow, the MM-BMSC interaction and the trafficking of MM cells from the bloodstream to distant bone locations is therefore crucial to design new, more effective therapies capable of overcoming the maladaptive interaction between BMSCs and MM and help in finding a cure for MM.