Affiliation:
1. From the University Medical Center Charite, Department of Hematology, Oncology and Tumorimmunology, Robert-Rössle-Klinik, Campus Buch; and Campus Virchow Klinikum, Humboldt University, Berlin, Germany.
Abstract
Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1α) 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-1α on MM cells. Thus, we were able to demonstrate that MIP-1α acts as a potent growth, survival, and chemotactic factor in MM cells. MIP-1α–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-1α–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-1α also directly affects cell signaling pathways mediating growth, survival, and migration in MM cells and provide evidence that MIP-1α might play a pivotal role in the pathogenesis of MM.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference25 articles.
1. Pathogenesis and management of bone lesions in multiple myeloma.;Bataille;Hematol Oncol Clin North Am.,1997
2. Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.;Kukita;Lab Invest.,1997
3. Macrophage inflammatory protein-1 alpha and IL-8 stimulate the motility but suppress the resorption of isolated rat osteoclasts.;Fuller;J Immunol.,1995
4. Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma.;Choi;Blood.,2000
5. Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease.;Choi;J Clin Invest.,2001
Cited by
198 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献