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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Rho family small GTPases control migration of hematopoietic progenitor cells into multicellular spheroids of bone marrow stroma cells.
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Rho family small GTPases control migration of hematopoietic progenitor cells into multicellular spheroids of bone marrow stroma cells.

机译:Rho家族的小GTPases控制着造血祖细胞向骨髓基质细胞多细胞球体的迁移。

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摘要

Seeding of hematopoietic progenitor cells (HPC) into the bone marrow requires a complex interaction between cell membrane and adhesion systems and cell signaling pathways. We established a multicellular, spheroid coculture model to study HPC migration in a three-dimensional stromal environment. Here, entry of primary CD34(+) cells into stroma cell spheroids was independent of the integrins very late antigen (VLA)-4, VLA-5, lymphocyte function-associated antigen-1, and the chemokine receptor CXCR4. Experiments using a panel of bacterial toxins selectively targeting key regulators of cellular locomotion, the Rho family small GTPases Rho, Rac, and Cdc42, revealed a considerable reduction or even abrogation of TF-1 cell migration without an increase of apoptosis or impairment of proliferation. Pertussis toxin, an inhibitor of Galpha(i) proteins, showed a similar effect. In some in vitro invasion assays, phosphatidylinositol-3 kinase (PI-3K) was shown to mediate Rac- and Cdc42-induced cell motility and invasion. However, inhibition of the PI-3K pathway by LY294002 did not impair TF-1 cell migration in our three-dimensional model system.
机译:造血祖细胞(HPC)播种到骨髓中需要细胞膜与粘附系统和细胞信号通路之间复杂的相互作用。我们建立了一个多细胞球状共培养模型,以研究HPC在三维基质环境中的迁移。在这里,原代CD34(+)细胞进入基质细胞球体的过程与整联蛋白极晚抗原(VLA)-4,VLA-5,淋巴细胞功能相关抗原-1和趋化因子受体CXCR4无关。使用选择性靶向细胞运动关键调节因子Rho家族的小GTPases Rho,Rac和Cdc42的一组细菌毒素进行的实验显示,TF-1细胞迁移可显着减少或消除,而不会增加细胞凋亡或增殖能力。百日咳毒素,一种Galpha(i)蛋白的抑制剂,显示出相似的作用。在某些体外侵袭试验中,磷脂酰肌醇3激酶(PI-3K)被证明可介导Rac和Cdc42诱导的细胞运动和侵袭。但是,在我们的三维模型系统中,LY294002对PI-3K通路的抑制作用不会损害TF-1细胞的迁移。

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