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Title: RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma
Authors: Azab, Abdel Kareem 
Azab, Feda 
Blotta, Simona 
Pitsillides, Costas 
Thompson, Brian D. 
Runnels, Judith M. 
Roccaro, Aldo Maria 
Ngo, Hai T. 
Melhem, Molly R. 
Sacco, Antonio 
Jia, Xiaoying 
Anderson, Kenneth Carl 
Lin, Charles P. 
Rollins, Barrett J. 
Ghobrial, Irène M. 
Major Field of Science: Medical and Health Sciences
Field Category: Clinical Medicine
Keywords: Cell adhesion;Multiple myeloma;Chemotaxis;Mice;Animal experimentation;Cells;Cytoskeleton
Issue Date: 16-Jul-2009
Source: Blood, 2009, vol. 114, no. 3, pp. 619-629
Volume: 114
Issue: 3
Start page: 619
End page: 629
Journal: Blood 
Abstract: The interaction of multiple myeloma (MM) cells with the bone marrow (BM) milieu plays a crucial role in MM pathogenesis. Stromal cell–derived factor-1 (SDF1) regulates homing of MM cells to the BM. In this study, we examined the role of RhoA and Rac1 GTPases in SDF1-induced adhesion and chemotaxis of MM. We found that both RhoA and Rac1 play key roles in SDF1-induced adhesion of MM cells to BM stromal cells, whereas RhoA was involved in chemotaxis and motility. Furthermore, both ROCK and Rac1 inhibitors reduced SDF1-induced polymerization of actin and activation of LIMK, SRC, FAK, and cofilin. Moreover, RhoA and Rac1 reduced homing of MM cells to BM niches. In conclusion, we characterized the role of RhoA and Rac1 GTPases in SDF1-induced adhesion, chemotaxis, and homing of MM cells to the BM, providing the framework for targeting RhoA and Rac1 GTPases as novel MM therapy
ISSN: 15280020
DOI: 10.1182/blood-2009-01-199281
Rights: © The American Society of Hematology
Type: Article
Affiliation: Massachusetts General Hospital 
Affiliation : Dana-Farber Cancer Institute 
Harvard University 
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