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

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 xe...

Full description

Saved in:
Bibliographic Details
Main Authors: Tao Du, Guanqun Ju, Shuai Wu, Zhongliang Cheng, Jun Cheng, Xiangyu Zou, Guangyuan Zhang, Shuai Miao, Guohua Liu, Yingjian Zhu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096836&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850026693926846464
author Tao Du
Guanqun Ju
Shuai Wu
Zhongliang Cheng
Jun Cheng
Xiangyu Zou
Guangyuan Zhang
Shuai Miao
Guohua Liu
Yingjian Zhu
author_facet Tao Du
Guanqun Ju
Shuai Wu
Zhongliang Cheng
Jun Cheng
Xiangyu Zou
Guangyuan Zhang
Shuai Miao
Guohua Liu
Yingjian Zhu
author_sort Tao Du
collection DOAJ
description 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.
format Article
id doaj-art-24d48a29cbb74a9ca3fb7ef3f44a6f67
institution DOAJ
issn 1932-6203
language English
publishDate 2014-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-24d48a29cbb74a9ca3fb7ef3f44a6f672025-08-20T03:00:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9683610.1371/journal.pone.0096836Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.Tao DuGuanqun JuShuai WuZhongliang ChengJun ChengXiangyu ZouGuangyuan ZhangShuai MiaoGuohua LiuYingjian ZhuIn 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096836&type=printable
spellingShingle Tao Du
Guanqun Ju
Shuai Wu
Zhongliang Cheng
Jun Cheng
Xiangyu Zou
Guangyuan Zhang
Shuai Miao
Guohua Liu
Yingjian Zhu
Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
PLoS ONE
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.
title_full Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
title_fullStr Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
title_full_unstemmed Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
title_short Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor.
title_sort microvesicles derived from human wharton s jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0096836&type=printable
work_keys_str_mv AT taodu microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT guanqunju microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT shuaiwu microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT zhongliangcheng microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT juncheng microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT xiangyuzou microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT guangyuanzhang microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT shuaimiao microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT guohualiu microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor
AT yingjianzhu microvesiclesderivedfromhumanwhartonsjellymesenchymalstemcellspromotehumanrenalcancercellgrowthandaggressivenessthroughinductionofhepatocytegrowthfactor