Myeloma Cells and Their Interactions With the Bone Marrow Endothelial Cells

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by a monoclonal proliferation of plasma cells in the bone marrow (BM), secretion of paraprotein in serum, development of osteolytic bone lesions and angiogenesis in the BM. In the BM, MM cells receive signals to survive and proliferate due to the existence of functional, mutual interactions between the MM cells and the BM stromal cells. This stroma not only offers protection against apoptosis and leads to growth stimulation, but also has a role in the clinical very relevant drug resistance. As such, it became clear that the BM stroma can also become a therapeutical target in addition to the MM cells. In the past, the BM fibroblasts were considered to be the main stromal cells that interact with the MM cells. However, since the observation of a myeloma associated angiogenesis in patients and in the 5TMM mouse model, it became clear that the endothelial cells (EC) are also an important participant of the BM stromal cells. BMEC are involved in the specific homing of MM cells and are a source of paracrine growth factors. In this review, the interaction between BMEC and MM cells will be discussed.