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.
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Authors | Suzanne Lentzsch, Margarete Gries, Martin Janz, Ralf Bargou, Bernd Dörken, Markus Y Mapara |
Journal | Blood
(Blood)
Vol. 101
Issue 9
Pg. 3568-73
(May 01 2003)
ISSN: 0006-4971 [Print] United States |
PMID | 12506012
(Publication Type: Journal Article)
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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
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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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