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

Official URL:https://doi.org/10.1182/blood-2002-08-2383
PubMed:View item in PubMed
Creators Name:Lentzsch, S. and Gries, M. and Janz, M. and Bargou, R. and Doerken, B. and Mapara, M.Y.
Journal Title:Blood
Journal Abbreviation:Blood
Page Range:3568-3573
Date:1 May 2003
Keywords:Androstadienes, Cell Division, Cell Survival, Chemokine CCL3, Chemokine CCL4, Chemokine Receptors, Cultured Tumor Cells, Cytokines, Enzyme Activation, Enzyme Inhibitors, Flavonoids, MAP Kinase Kinase 1, MAP Kinase Signaling System, Macrophage Inflammatory Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Multiple Myeloma, Neoplasm Proteins, Osteolysis, Phosphatidylinositol 3-Kinases, Phosphorylation, Post-Translational Protein Processing, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract:Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1{alpha}) 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-1{alpha} on MM cells. Thus, we were able to demonstrate that MIP-1{alpha} acts as a potent growth, survival, and chemotactic factor in MM cells. MIP-1{alpha}–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-1{alpha}–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-1{alpha} also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and provide evidence that MIP-1{alpha} might play a pivotal role in the pathogenesis of MM.
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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