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

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.

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

“…Dickkopf (DKK) acts as an antagonist of WNT signaling via binding to its co-receptor LRP (91,92). Interestingly, the MSC-induced pro-tumorigenic effect seems to be regulated by the Wnt/β-catenin signaling in breast cancer (93.94), whereas the inhibition of tumor proliferation occurs by MSC induced secretion of DKK-1, an inhibitor of the same pathway (95,96). Furthermore, the MSC-derived CM exerts its effect by targeting the Wnt/β-catenin signaling pathway (97,98).…”

Value of the level of methylation of RASSF1A and WIF-1 in tissue and serum in neoadjuvant chemotherapeutic assessment for advanced breast cancer

“…C-myc and cyclin D1, as two important downstream target genes, regulate the cell division cycle ( 15 ). Not only is E-cadherin an important effector molecular in this signal pathway, but also a key factor in the invasion, metastasis and recurrence of breast cancer ( 16 ). As a major tumor suppressor gene of Wnt pathways, WIF-1 which is highly methylated or expresses a low level of mRNA can significantly affect the occurrence and development of breast cancer ( 17 ).…”

Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse Xenograft model

“…It has been reported that human BMSCs play a fundamental role in breast cancer pathogenesis [20][21][22] . BMSCs are recruited to the stroma of the primary tumor site, where they might facilitate breast cancer cell invasion and distant metastasis [23] .…”