title: Macrophage inflammatory protein 1-alpha (MIP-1 alpha ) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells.
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.
authors.affiliation: University Medical Center Charite, Department of Hematology, Oncology and Tumorimmunology, Robert-Rössle-Klinik, Campus Buch, Humboldt University, Berlin, Germany. lentzsch@rrk.charite-buch.de
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lentzsch
authors.forename: Margarete
authors.initials: M
authors.lastname: Gries
authors.forename: Martin
authors.initials: M
authors.lastname: Janz
authors.forename: Ralf
authors.initials: R
authors.lastname: Bargou
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Markus Y
authors.initials: MY
authors.lastname: Mapara
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002455:Cell Division; D002470:Cell Survival; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010014:Osteolysis / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D048369:MAP Kinase Kinase 1; D019402:Macrophage Inflammatory Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019707:Receptors, Chemokine; D000077191:Wortmannin; C080633:macrophage inflammatory protein 1alpha receptor; C494918:AKT1 protein, human; C482125:MAP2K1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one