RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma.
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.
Azab
Abdel Kareem
AK
Medical Oncology, Dana-Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, 44 Binney Street, Boston, MA, USA.
Azab
Feda
F
Blotta
Simona
S
Pitsillides
Costas M
CM
Thompson
Brian
B
Runnels
Judith M
JM
Roccaro
Aldo M
AM
Ngo
Hai T
HT
Melhem
Molly R
MR
Sacco
Antonio
A
Jia
Xiaoying
X
Anderson
Kenneth C
KC
Lin
Charles P
CP
Rollins
Barrett J
BJ
Ghobrial
Irene M
IM
D000818:Animals; D001853:Bone Marrow; D002448:Cell Adhesion; D054377:Chemokine CXCL12 / Q000502:physiology*; D002633:Chemotaxis; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000473:pathology*; D017154:Stromal Cells; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D054377:Chemokine CXCL12; D003598:Cytoskeletal Proteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein