title: Microvesicles secreted from human multiple myeloma cells promote angiogenesis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China [2] Department of Hematology, Affiliated Hospital of Taishan Medical College, Taian 271000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Zhu
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Pin-hui
authors.initials: PH
authors.lastname: Wu
authors.affiliation: Department of Hematology, Wuhan Central Hospital, Wuhan 430022, China.
authors.forename: Hong-xiang
authors.initials: HX
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Zhi-chao
authors.initials: ZC
authors.lastname: Chen
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qiu-bai
authors.initials: QB
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D022142:Secretory Vesicles / Q000473:pathology*; D014471:Umbilical Veins / Q000473:pathology