Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma
| Autor: | Gang Song, Yinping Tong, Yubin Mao, Jiahui Yuan, Congcong Yan, Tianhui Hu, Weiwei Wang, Wei Zhong, Bing Zhang, Shaoping Hu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Beta-catenin Ginsenosides Blotting Western Mice Nude MSCs Apoptosis Biology Metastasis Cholangiocarcinoma Cell Line Tumor medicine metastasis Animals Humans Progenitor cell Neoplasm Metastasis Wnt Signaling Pathway Cells Cultured Cell Proliferation Mice Inbred BALB C Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction Mesenchymal stem cell Wnt signaling pathway chemoresistance Mesenchymal Stem Cells β-catenin medicine.disease Xenograft Model Antitumor Assays Tumor Burden Transplantation Gene Expression Regulation Neoplastic Oncology Bile Duct Neoplasms Cell culture Drug Resistance Neoplasm Culture Media Conditioned Cancer cell biology.protein Cancer research Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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 β-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/β-catenin signaling pathway. hUC-MSCs or MSCs-CM stimulated Wnt activity by promoting the nuclear translocation of β-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/β-catenin signaling. |
| Databáze: | OpenAIRE |
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