Mutliple Myeloma-derived Microvesicles: A Novel Way to Promote Myeloma Angiogenesis
|School||Huazhong University of Science and Technology|
|Keywords||multiple myeloma (MM) Microvesicle (MV) endothelial cells (ECs) angiogenesis|
Objective Angiogenesis plays an essential role in multiple myeloma growth, invasiveness, and metastasis. The specific mechanism of angiogenesis in multiple myeloma (MM) is still unknown. The objective of present study was to investigate the effect of microvesicle (MV) derived from multiple myeloma cells on angiogenesis of endothelial cells (ECs) in the tumor microenvirnment, and to investigate the mechanisms involved. Methods MTT assay, transwell migration assay and tube formation assay were used to study the infection of the Microvesicle (MV) from human multiple myeloma to EAHY926 cells in microenvirnment,as well as RT-polymerase chain reaction (RT-PCR), Enzyme- linked immunosorbent assay (Elisa), Confocal and Flow cytometry methods were employed to study the mechanisms involved.Results Multiple myeloma (RPMI8226)-derived microvesicles promoted EAHY926 cells proliferation, migration and tube formation in vivo and vitro. Confocal and Flow cytometry showed that MM-MV fused with EAHY926 cells. After co-cultured with MM-MV, EAHY926 cells proliferated quickly at 12h, 24h, 36h and 48h (MV vs control group, P<0.05). EAHY926 cells in MV group had more migration at 12h, 24h and 36h (P<0.05). However, there were no differences in EAHY926 cells migration between MV and control groups at 48h (P>0.05). In vitro, there were more tube formation in MV group than control group at 9h and 12h, P<0.05); Tube numbers were similar in MV and control groups (P>0.05). In vivo, we found more function tubes in MV group compared to control group (P<0.05). The expression of IL-6, VEGF mRNA were higher in MV group than control group. Elisa was to detect IL-6 and VEGF secretion. We found that the amount of IL-6, VEGF was obviously increased in MV group than control group (P<0.05). However VEGF secretion had no difference between MV and control groups at 48h (P>0.05). we tried to probe the mechanism, and we found MM-MV fused with EAHY926 and MM cells in Confocal and Flow cytometry assy. The result illustrated the fusion with target cells was general, and one type of action. MM-MV promoted EAHY926 cells to secret IL-6, VEGF by fusing with EAHY926 cells directly, and further promoted MM angiogenesis.Conclusions Multiple myeloma cells derived microvesicle promoted tumor endothelial cells angiogensis: a novel way to promote myeloma angiogenesis.