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Blood, 16 July 2009, Vol. 114, No. 3, pp. 619-629. Prepublished online as a Blood First Edition Paper on May 14, 2009; DOI 10.1182/blood-2009-01-199281. This Article Full Text (PDF) Supplemental Tables, Figures, and Videos All Versions of this Article: blood-2009-01-199281v1 114/3/619    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Azab, A. K. Articles by Ghobrial, I. M. Search for Related Content PubMed PubMed Citation Articles by Azab, A. K. Articles by Ghobrial, I. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 13, 2009 Accepted May 5, 2009 Rho-A and Rac-1 GTPases play major and differential roles in SDF1-induced cell adhesion and chemotaxis in multiple myeloma Abdel Kareem Azab, Feda Azab, Simona Blotta, Costas M. Pitsillides, Brian Thompson, Judith M. Runnels, Aldo M. Roccaro, Hai T. Ngo, Molly R. Melhem, Antonio Sacco, Xiaoying Jia, Kenneth C. Anderson, Charles P. Lin, Barrett J. Rollins, and Irene M. Ghobrial* Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States * Corresponding author; email: irene_ghobrial{at}dfci.harvard.edu. The interaction of MM cells with the bone marrow (BM) milieu plays a crucial role in MM pathogenesis and drug resistance. Stromal cell-derived factor-1 (SDF-1) regulates chemotaxis and 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 cells. We found that both RhoA and Rac1 GTPases play key roles in SDF1-induced adhesion of MM cells to extracellular-matrix and BM-stromal-cells, while only RhoA was involved in chemotaxis and motility of MM cells. Furthermore, both ROCK and Rac1 inhibitors reduced SDF1-induced polymerization of actin and activation of LIMK, SRC, FAK and Cofilin, accounting for the similar role of RhoA and Rac1 in MM cell adhesion, but only ROCK inhibitor reduced the activation of MLC, associated with the differential role of RhoA in MM cell motility and chemotaxis. Moreover, both inhibitors reduced the homing of MM cells to BM niches; however, the ROCK inhibitor showed a more profound effect. In conclusion, we characterized 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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