RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma
RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma
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DOI：
10.1182/blood-2009-01-199281
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发表时间：
2009-07-16
期刊：
影响因子：
20.3
通讯作者：
Ghobrial, Irene M.
中科院分区：
文献类型：
--
作者：
Azab, Abdel Kareem;Azab, Feda;Ghobrial, Irene M.
多发性骨髓瘤 (MM) 细胞与骨髓 (BM) 环境的相互作用在 MM 发病机制中起着至关重要的作用。基质细胞衍生因子 1 (SDF1) 调节 MM 细胞归巢至 BM。在这项研究中，我们研究了 RhoA 和 Rac1 GTPases 在 SDF1 诱导的 MM 粘附和趋化中的作用。我们发现RhoA和Rac1在SDF1诱导的MM细胞与BM基质细胞的粘附中发挥关键作用，而RhoA参与趋化性和运动性。此外，ROCK 和 Rac1 抑制剂均可减少 SDF1 诱导的肌动蛋白聚合以及 LIMK、SRC、FAK 和 cofilin 的激活。此外，RhoA 和 Rac1 减少了 MM 细胞向 BM 微环境的归巢。总之，我们表征了 RhoA 和 Rac1 GTPases 在 SDF1 诱导的粘附、趋化性和 MM 细胞归巢至 BM 中的作用，为靶向 RhoA 和 Rac1 GTPases 作为新型 MM 治疗提供了框架。 （血。2009；114：619-629）
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. (Blood. 2009; 114: 619-629)