title: RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma.
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.
authors.affiliation: Medical Oncology, Dana-Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, 44 Binney Street, Boston, MA, USA.
authors.forename: Abdel Kareem
authors.initials: AK
authors.lastname: Azab
authors.forename: Feda
authors.initials: F
authors.lastname: Azab
authors.forename: Simona
authors.initials: S
authors.lastname: Blotta
authors.forename: Costas M
authors.initials: CM
authors.lastname: Pitsillides
authors.forename: Brian
authors.initials: B
authors.lastname: Thompson
authors.forename: Judith M
authors.initials: JM
authors.lastname: Runnels
authors.forename: Aldo M
authors.initials: AM
authors.lastname: Roccaro
authors.forename: Hai T
authors.initials: HT
authors.lastname: Ngo
authors.forename: Molly R
authors.initials: MR
authors.lastname: Melhem
authors.forename: Antonio
authors.initials: A
authors.lastname: Sacco
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jia
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.forename: Barrett J
authors.initials: BJ
authors.lastname: Rollins
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
mesh_terms: 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*
chemical_list: D054377:Chemokine CXCL12; D003598:Cytoskeletal Proteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein