RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-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, Irene M. Ghobrial

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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 ofMMcells toBMniches. 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.

Original languageEnglish
Pages (from-to)619-629
Number of pages11
JournalBlood
Volume114
Issue number3
DOIs
StatePublished - 2009

Fingerprint

Dive into the research topics of 'RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma'. Together they form a unique fingerprint.

Cite this