Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/β-catenin signaling pathway
2016
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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