Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/β-catenin signaling pathway

Li,Min; Cai,Hui; Yang,Ya; Zhang,Jia; Sun,Kai; Yan,Yan; Qu,Hangying; Wang,Weiwei; Wang,Jiansheng; Duan,Xiaoyi

doi:10.3892/or.2016.4853

Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/β-catenin signaling pathway

Authors:
- Min Li
- Hui Cai
- Ya Yang
- Jia Zhang
- Kai Sun
- Yan Yan
- Hangying Qu
- Weiwei Wang
- Jiansheng Wang
- Xiaoyi Duan
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Affiliations: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, The Third Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China, Department of Medical Oncology, The Second Hospital of Lanzhou, Lanzhou, Gansu 730000, P.R. China, Department of Histology and Embryology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: June 3, 2016 https://doi.org/10.3892/or.2016.4853
Pages: 936-944

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Abstract

In recent years, mesenchymal stem cells (MSCs), which possess the ability to specifically home to tumor sites, with the potential of multi-directional differentiation and low immunogenicity, have been reported to inhibit the growth of various types of tumors. In the present study, we isolated MSCs from the rib perichondrium (PMSCs). By comparing PMSCs with bone marrow‑derived mesenchymal stem cells (BMSCs), we demonstrated that PMSCs present biological characteristics similar to those of BMSCs. Furthermore, we explored the effect and antitumor mechanism of PMSCs in rat SHZ-88 breast cancer cells. The growth, migration and invasion of the SHZ-88 cells were significantly inhibited, and the Wnt/β-catenin pathway and its target genes were downregulated in the SHZ-88 cells by PMSC-conditioned medium. The expression level of dickkopf-1 (DKK-1) was higher in the PMSCs than that noted in the SHZ-88 cells. Neutralization of DKK-1 in the PMSC‑conditioned medium attenuated the inhibitory effects of PMSCs on SHZ-88 cells. Therefore, PMSC-secreted DKK-1 is involved in the inhibition of SHZ-88 cell growth, migration and invasion, via the Wnt/β‑catenin signaling pathway. In addition, we demonstrated that PMSCs inhibited the growth of breast cancer in vivo and prolonged the survival time of tumor‑bearing rats. PMSCs inhibited the growth of transplanted breast tumors through the Wnt/β-catenin signaling pathway. In conclusion, our data confirmed that MSCs derived from the perichondrium present biological characteristics similar to those of BMSCs and inhibit the growth of breast cancer cells through the Wnt/β-catenin signaling pathway in vitro and in vivo. DKK-1 secreted by PMSCs played a vital role in controlling the Wnt/β-catenin signaling pathway in breast cancer.

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