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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.
AuthorsSuzanne Lentzsch, Margarete Gries, Martin Janz, Ralf Bargou, Bernd Dörken, Markus Y Mapara
JournalBlood (Blood) Vol. 101 Issue 9 Pg. 3568-73 (May 01 2003) ISSN: 0006-4971 [Print] United States
PMID12506012 (Publication Type: Journal Article)
Chemical References
  • Androstadienes
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines
  • Enzyme Inhibitors
  • Flavonoids
  • Macrophage Inflammatory Proteins
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Receptors, Chemokine
  • macrophage inflammatory protein 1alpha receptor
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Wortmannin
Topics
  • Androstadienes (pharmacology)
  • Cell Division
  • Cell Survival
  • Chemokine CCL3
  • Chemokine CCL4
  • Cytokines (metabolism)
  • Enzyme Activation
  • Enzyme Inhibitors (pharmacology)
  • Flavonoids (pharmacology)
  • Humans
  • MAP Kinase Kinase 1
  • MAP Kinase Signaling System (physiology)
  • Macrophage Inflammatory Proteins (physiology)
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
  • Mitogen-Activated Protein Kinases (metabolism)
  • Multiple Myeloma (metabolism, pathology)
  • Neoplasm Proteins (metabolism)
  • Osteolysis (metabolism)
  • Phosphatidylinositol 3-Kinases (physiology)
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
  • Proto-Oncogene Proteins (antagonists & inhibitors, physiology)
  • Proto-Oncogene Proteins c-akt
  • Receptors, Chemokine (metabolism)
  • Signal Transduction (physiology)
  • Tumor Cells, Cultured (cytology, metabolism)
  • Wortmannin

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