Cancer Res:HIF-2α通过调节CXCL12/CXCR4和CCR1促进多发性骨髓瘤浆细胞播散

2017-11-01 MedSci MedSci原创

多发性骨髓瘤疾病进展和复发的主要原因是多发性骨髓瘤浆细胞重新进入循环系统以及在骨髓中进行播散。骨髓缺氧增加与多发性骨髓瘤浆细胞再循环增加有关。CANCER RES近期发表了一篇文章,研究在慢性缺氧过程中,HIF-2α活化是否可以克服基质分泌CXCL12提供的骨髓抑制信号,从而促进多发性骨髓瘤浆细胞播散。

多发性骨髓瘤疾病进展和复发的主要原因是多发性骨髓瘤浆细胞重新进入循环系统以及在骨髓中进行播散。骨髓缺氧增加与多发性骨髓瘤浆细胞再循环增加有关。CANCER RES近期发表了一篇文章,研究在慢性缺氧过程中,HIF-2α活化是否可以克服基质分泌CXCL12提供的骨髓抑制信号,从而促进多发性骨髓瘤浆细胞播散。

研究结果表明,在体外实验中,HIF-2α上调多发性骨髓瘤浆细胞CXCL12表达,降低向CXCL12的迁移能力,减少向间充质干细胞粘附。作者还发现HIF-2α可以强力诱导多发性骨髓瘤浆细胞CCR1细胞因子受体表达。CCR1活化可以诱导多发性骨髓瘤浆细胞向CCL3迁移并抑制多发性骨髓瘤浆细胞向CXCL2的迁移反应。此外,多发性骨髓瘤浆细胞CCR1表达增加与新发的多发性骨髓瘤患者不良预后有关,且与这些患者循环多发性骨髓瘤浆细胞增加有关。

文章最后认为,该研究结果表明缺氧介导的CCR1上调促进多发性骨髓瘤浆细胞从骨髓中迁移出来。靶向CCR1可能为预防多发性骨髓瘤播散和复发提供理想的治疗方案。

原始出处:
Kate Vandyke,Mara N.Zeissig,et al.HIF-2α Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1.CLIN CACNER RES.October 2017 doi:10.1158/0008-5472.CAN-17-0115

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    2018-08-11 jml2009
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    2017-11-24 wetgdt
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    2017-11-03 chenwq09
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    2017-11-03 wrj0126
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    2017-11-01 明月清辉

    谢谢分享.学习了

    0

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