title: Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
abstract: In our previous study, microvesicles (MVs) released from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) retard the growth of bladder cancer cells. We would like to know if MVs have a similar effect on human renal cell carcinoma (RCC). By use of cell culture and the BALB/c nu/nu mice xeno-graft model, the influence of MVs upon the growth and aggressiveness of RCC (786-0) was assessed. Cell counting kit-8 (CCK-8) assay, incidence of tumor, tumor size, Ki-67 or TUNEL staining was used to evaluate tumor cell growth in vitro or in vivo. Flow cytometry assay (in vitro) or examination of cyclin D1 expression (in vivo) was carried out to determine the alteration of cell cycle. The aggressiveness was analyzed by Wound Healing Assay (in vitro) or MMP-2 and MMP-9 expression (in vivo). AKT/p-AKT, ERK1/2/p-ERK1/2 or HGF/c-MET expression was detected by real-time PCR or western blot. Our data demonstrated that MVs promote the growth and aggressiveness of RCC both in vitro and in vivo. In addition, MVs facilitated the progression of cell cycle from G0/1 to S. HGF expression in RCC was greatly induced by MVs, associated with activation of AKT and ERK1/2 signaling pathways. RNase pre-treatment abrogated all effects of MVs. In summary, induction of HGF synthesis via RNA transferred by MVs activating AKT and ERK1/2 signaling is one of crucial contributors to the pro-tumor effect.
authors.affiliation: Department of Urology, Henan Provincial People's Hospital, Zhengzhou, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Ju
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China; Department of Urology, Qingdao Municipal Hospital, Qingdao, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Urology, Nantong Tongzhou People's Hospital, Jiangsu Province, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Miao
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002450:Cell Communication; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000737:chemistry; D019938:Cyclin D1 / Q000378:metabolism; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction; D059631:Wharton Jelly / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned; C066855:HGF protein, human; D019938:Cyclin D1; D017228:Hepatocyte Growth Factor; D012260:Ribonucleases