文章：

C3a和C5a通过激活Nrf2促进骨髓瘤细胞转移

C3a and C5a facilitates the metastasis of myeloma cells by activating Nrf2 

原文发布日期：2020-09-02 

英文摘要：

Multiple myeloma (MM) is still an incurable hematological malignancy, with even poorer prognosis in MM patients with distant invasion. The present study was designed to explore the effects of C3a and C5a on the migration, invasion, and adhesion of MM tumor cells and to investigate the underlying mechanisms. As a result, the levels of C3a and C5a in plasma of MM patients were significantly higher than those of healthy donors. Consistently, the expression of C3a and C5a receptors on myeloma cells of MM patients was also significantly higher than that on sorted plasma cells of normal donors. C3a and C5a have been confirmed to increase the migration, invasion and adhesion of MM cell lines by activating the MEK/ERK pathway and increasing the nuclear transfer of Nrf2 in vitro. Moreover, the MM cell line U266 with Nrf2 downregulation was incubated with C3a and C5a, followed by injection into the tail vein of NOD-SCID mice. We found that Nrf2 downregulation attenuated the migration of anaphylatoxin C3a and C5a to MM tumor cells in bone marrow, liver and lung in vivo. In conclusion, our results indicate that activation of the complement cascade in MM patients may contribute to the migration, invasion and adhesion of MM cells, and this type of tumor cells dissemination in MM is, at least partially, regulated by Nrf2. Thereby, complement suppression or Nrf2 downregulation might offer a novel therapeutic opportunity for MM. 

摘要翻译： 

多发性骨髓瘤（MM）仍是一种无法治愈的血液系统恶性肿瘤，发生远处侵袭的MM患者预后更差。本研究旨在探讨C3a和C5a对MM肿瘤细胞迁移、侵袭与黏附能力的影响及其作用机制。结果显示：MM患者血浆中C3a和C5a水平显著高于健康供体；与此一致的是，MM患者骨髓瘤细胞表面C3a与C5a受体的表达量也显著高于正常供体分选后的浆细胞。经体外实验证实，C3a和C5a通过激活MEK/ERK通路并促进Nrf2核转移，可增强MM细胞系的迁移、侵袭和黏附能力。此外，将Nrf2下调的MM细胞系U266与C3a和C5a共培养后，通过尾静脉注射至NOD-SCID小鼠体内，发现Nrf2下调可减弱过敏毒素C3a和C5a在体内促进MM肿瘤细胞向骨髓、肝脏和肺部迁移的作用。综上所述，我们的研究结果表明：MM患者体内补体级联反应的激活可能促进肿瘤细胞的迁移、侵袭与黏附，且这种肿瘤细胞扩散过程至少部分受Nrf2调控。因此，抑制补体或下调Nrf2可能为MM治疗提供新策略。

原文链接：

C3a and C5a facilitates the metastasis of myeloma cells by activating Nrf2