Macrophage inflammatory protein 1-alpha (MIP-1α) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells

Recently, it has been demonstrated that macrophage inflammatory protein 1-alpha (MIP-1alpha) is crucially involved in the development of osteolytic bone lesions in multiple myeloma (MM). The current study was designed to determine the direct effects of MIP-1alpha on MM cells. Thus, we were able to demonstrate that MIP-1alpha acts as a potent growth, survival, and chemotactic factor in MM cells. MIP-1alpha-induced signaling involved activation of the AKT/protein kinase B (PKB) and the mitogen-activated protein kinase (MAPK) pathway. In addition, inhibition of AKT activation by phosphatidylinositol 3-kinase (PI3-K) inhibitors did not influence MAPK activation, suggesting that there is no cross talk between MIP-1alpha-dependent activation of the PI3-K/AKT and extracellular-regulated kinase (ERK) pathway. Our data suggest that besides its role in development of osteolytic bone destruction, MIP-1alpha also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and provide evidence that MIP-1alpha might play a pivotal role in the pathogenesis of MM. (C) 2003 by The American Society of Hematology.