Microvesicles secreted from human multiple myeloma cells promote angiogenesis
Microvesicles secreted from human multiple myeloma cells promote angiogenesis
复制标题
人多发性骨髓瘤细胞分泌的微泡促进血管生成
DOI：
10.1038/aps.2013.141
复制
发表时间：
2014-02-01
影响因子：
8.2
通讯作者：
Li, Qiu-bai
中科院分区：
文献类型：
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作者：
Liu, Yan;Zhu, Xiao-jian;Li, Qiu-bai
目的：研究人多发性骨髓瘤（MM）细胞是否分泌微泡（Microvesicles，MVs）以及MM细胞分泌的MVs是否促进血管生成。使用hy 926人脐静脉细胞。从RPMI 8226细胞中分离的MV在激光共聚焦显微镜、电子显微镜和流式细胞仪下表征。MM-MV和EA的融合。hy 926细胞在共聚焦显微镜下观察，CD 138转移到EA。hy 926细胞经流式细胞仪检测。EA的增殖、侵袭和管形成。hy 926细胞的体外培养分别采用MTT法、transwell迁移实验和试管形成实验。EA的血管化。hy 926细胞的体内研究使用Matrigel plug assay。结果：RPMI 8226细胞的MM-MVs呈杯状，直径约100-1000 nm。大多数MM-MV表达磷脂酰丝氨酸和骨髓瘤细胞标志物CD 138，证实它们来源于骨髓瘤细胞。添加到EA后。hy 926细胞，MM-MVs可将CD 138分子转移到内皮细胞上，并在体内外显著刺激内皮细胞增殖、侵袭、分泌IL-6和VEGF两种骨髓瘤血管生成关键因子，并形成管状结构。结论：MM-MVs在MM细胞中存在，支持MM-MVs是骨髓瘤血管生成的新介质的观点，并可作为MM治疗的靶点。
Aim:To investigate whether human multiple myeloma (MM) cells secrete microvesicles (MVs) and whether the MVs secreted from MM cells (MM-MVs) promote angiogenesis.Methods:RPMI8226 human MM cells and EA. hy926 human umbilical vein cells were used. MVs isolated from RPMI8226 cells were characterized under laser confocal microscopy, electron microscopy and with flow cytometry. The fusion of MM-MVs and EA. hy926 cells was studied under confocal microscopy, and the transfer of CD138 to EA. hy926 cells was demonstrated with flow cytometry. The proliferation, invasion and tube formation of EA. hy926 cells in vitro were evaluated using MTT, transwell migration and tube formation assays, respectively. The vasculization of EA. hy926 cells in vivo was studied using Matrigel plug assay. The expression of IL-6 and VEGF was analyzed with PCR and ELISA.Results:MM-MVs from the RPMI 8226 cells had the characteristic cup-shape with diameter of 100–1000 nm. Most of the MM-MVs expressed phosphatidylserine and the myeloma cell marker CD138, confirming that they were derived from myeloma cells. After added to EA. hy926 cells, the MM-MVs transferred CD138 to the endothelial cells and significantly stimulated the endothelial cells to proliferate, invade, secrete IL-6 and VEGF, two key angiogenic factors of myeloma, and form tubes in vitro and in vivo.Conclusion:Our results confirm the presence of MVs in MM cells and support the idea that MM-MVs are newfound mediators for myeloma angiogenesis and may serve as a therapeutic target to treat MM.