TY - JOUR
T1 - RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma
AU - Azab, Abdel Kareem
AU - Azab, Feda
AU - Blotta, Simona
AU - Pitsillides, Costas M.
AU - Thompson, Brian
AU - Runnels, Judith M.
AU - Roccaro, Aldo M.
AU - Ngo, Hai T.
AU - Melhem, Molly R.
AU - Sacco, Antonio
AU - Jia, Xiaoying
AU - Anderson, Kenneth C.
AU - Lin, Charles P.
AU - Rollins, Barrett J.
AU - Ghobrial, Irene M.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2009-01-199281
DO - 10.1182/blood-2009-01-199281
M3 - Article
C2 - 19443661
AN - SCOPUS:69249087807
SN - 0006-4971
VL - 114
SP - 619
EP - 629
JO - Blood
JF - Blood
IS - 3
ER -