Identification of the migratory subpopulation in the multiple myeloma tumor clone and the involvement of CD44v, MMP-9 and uPA in the bone marrow homing of this population.

Multiple myeloma (MM) cells in the bone marrow (BM) display a heterogenous expression of the plasma cell maturation markers CD45 and CD49e. Based on the expression of these two antigens, MM cells can be grouped into different subpopulations. It is however not known which subpopulation(s) initially enter(s) the BM and induce(s) the disease. We will identify this migratory subpopulation (s) in the experimental 5T mouse model of MM by sorting the different CD45CD49e subpopulations and by analyzing their BM homing and MM inducing capacities. The migratory and non-migratory populations will be analyzed for differential expression of key molecules. We will in particular focus on the involvement of CD44 variants (CD44v) in the adhesion to and transendothelial migration of the tumor cells through BM endothelial cells. In addition, we will investigate the association between CD44v and matrix metalloproteinases, the involvement of urokinase plasminogen activator in the invasive capacity of the migratory MM cells.