PMID- 26474277
OWN - NLM
STAT- MEDLINE
DCOM- 20160927
LR  - 20220408
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 39
DP  - 2015 Dec 8
TI  - Involvement of Wnt/beta-catenin signaling in the mesenchymal stem cells promote 
      metastatic growth and chemoresistance of cholangiocarcinoma.
PG  - 42276-89
LID - 10.18632/oncotarget.5514 [doi]
AB  - Mesenchymal stem cells (MSCs) are multi-potent progenitor cells with ability to 
      differentiate into multiple lineages, including bone, cartilage, fat, and 
      muscles. Recent research indicates that MSCs can be efficiently recruited to 
      tumor sites, modulating tumor growth and metastasis. However, the underlying 
      molecular mechanisms are not fully understood. Here, we first demonstrated that 
      human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), when mixed with 
      human cholangiocarcinoma cell lines QBC939 in a xenograft tumor model, 
      significantly increased the cancer cells proliferation and metastatic potency. 
      MSCs and their conditioned media (MSC-CM) could improve the drug resistance of 
      tumor when the compound K (CK) as an anti-cancer drug, a major intestinal 
      bacterial metabolite of panaxoside, was administered to xenograft tumor mice. 
      Furthermore, MSCs greatly increased the colony formation and invasion of 
      cholangiocarcinoma cells QBC939 and Mz-ChA-1. Immunochemistry studies of 
      cholangiocarcinoma tissue chips and transplantation tumor from nude mice showed 
      that the expression of beta-catenin was important for cholangiocarcinoma 
      development. We further demonstrated that MSCs and MSCs-CM could promote 
      proliferation and migration of cholangiocarcinoma cells through targeting the 
      Wnt/beta-catenin signaling pathway. hUC-MSCs or MSCs-CM stimulated Wnt activity by 
      promoting the nuclear translocation of beta-catenin, and up-regulated Wnt target 
      genes MMPs family, cyclin D1 and c-Myc. Together, our studies highlight a 
      critical role for MSCs on cancer metastasis and indicate MSCs promote metastatic 
      growth and chemoresistance of cholangiocarcinoma cells via activation of 
      Wnt/beta-catenin signaling.
FAU - Wang, Weiwei
AU  - Wang W
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Zhong, Wei
AU  - Zhong W
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Yuan, Jiahui
AU  - Yuan J
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Yan, Congcong
AU  - Yan C
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Hu, Shaoping
AU  - Hu S
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Tong, Yinping
AU  - Tong Y
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Mao, Yubin
AU  - Mao Y
AD  - Department of Basic Medicine, Medical College of Xiamen University, Xiamen 
      361102, China.
FAU - Hu, Tianhui
AU  - Hu T
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
FAU - Zhang, Bing
AU  - Zhang B
AD  - Department of Basic Medicine, Medical College of Xiamen University, Xiamen 
      361102, China.
FAU - Song, Gang
AU  - Song G
AD  - Cancer Research Center, Medical College of Xiamen University, Xiamen 361102, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Ginsenosides)
RN  - A9RLM212CY (ginsenoside M1)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Bile Duct Neoplasms/drug therapy/*genetics/metabolism
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Cells, Cultured
MH  - Cholangiocarcinoma/drug therapy/*genetics/metabolism
MH  - Culture Media, Conditioned/pharmacology
MH  - Drug Resistance, Neoplasm/drug effects/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Ginsenosides/pharmacology
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microscopy, Confocal
MH  - Neoplasm Metastasis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Burden/drug effects/genetics
MH  - Wnt Signaling Pathway/*genetics
MH  - Xenograft Model Antitumor Assays
PMC - PMC4747224
OTO - NOTNLM
OT  - MSCs
OT  - chemoresistance
OT  - cholangiocarcinoma
OT  - metastasis
OT  - beta-catenin
COIS- CONFLICTS OF INTEREST The authors declare no conflict of interests.
EDAT- 2015/10/17 06:00
MHDA- 2016/09/28 06:00
PMCR- 2015/12/08
CRDT- 2015/10/17 06:00
PHST- 2015/04/17 00:00 [received]
PHST- 2015/09/05 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2016/09/28 06:00 [medline]
PHST- 2015/12/08 00:00 [pmc-release]
AID - 5514 [pii]
AID - 10.18632/oncotarget.5514 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Dec 8;6(39):42276-89. doi: 10.18632/oncotarget.5514.