Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor

• Published in: PloS one 2014-05, Vol.9 (5), p.e96836-e96836
• Main Authors: Du, Tao, Ju, Guanqun, Wu, Shuai, Cheng, Zhongliang, Cheng, Jun, Zou, Xiangyu, Zhang, Guangyuan, Miao, Shuai, Liu, Guohua, Zhu, Yingjian
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Animals; Assaying; Bladder; Bladder cancer; Bone marrow; c-Met protein; Cancer; Cell Communication; Cell culture; Cell cycle; Cell Cycle - drug effects; Cell Proliferation - drug effects; Cholecystokinin; Culture Media, Conditioned - chemistry; Cyclin D1; Cyclin D1 - metabolism; Cytometry; Ethics; Flow Cytometry; Gelatinase A; Gelatinase B; Growth factors; Hepatocyte growth factor; Hepatocyte Growth Factor - metabolism; Hostages; Humans; In vivo methods and tests; Kidney - metabolism; Kidney cancer; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Laboratory animals; Leukemia; Male; Medical research; Medicine; Medicine and Health Sciences; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Metastasis; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Phosphorylation; Proteins; Real-Time Polymerase Chain Reaction; Renal cell carcinoma; Ribonuclease; Ribonucleases - metabolism; Ribonucleic acid; RNA; Rodents; Signal Transduction; Signaling; Stem cell transplantation; Stem cells; Streptococcus infections; Transcription; Tumors; Urinary bladder; Urology; Wharton Jelly - metabolism; Wound Healing; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096836

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.