Human Mesenchymal Stem Cells Derived from the Placenta and Chorion Suppress the Proliferation while Enhancing the Migration of Human Breast Cancer Cells

Abstract

Background. Breast cancer is the most frequently diagnosed malignancy among women, resulting from abnormal proliferation of mammary epithelial cells. The highly vascularized nature of breast tissue leads to a high incidence of breast cancer metastases, resulting in a poor survival rate. Previous studies suggest that human mesenchymal stem cells (hMSCs) play essential roles in the growth, metastasis, and drug responses of many cancers, including breast cancer. However, hMSCs from different sources may release different combinations of cytokines that affect breast cancer differently. Methods. In this study, we have isolated hMSCs from the placenta (PL-hMSCs) and the chorion (CH-hMSCs) and determined how these hMSCs affect the proliferation, migration, invasion, and gene expression of two human breast cancer cells, MCF-7 and MDA-MB-231, as well as the possible mechanisms underlying those effects. Results. The results showed that the soluble factors derived from PL-hMSCs and CH-hMSCs inhibited the proliferation of MCF-7 and MDA-MB-231 cells but increased the migration of MDA-MB-231 cells. The study of gene expression showed that PL-hMSCs and CH-hMSCs downregulated the expression levels of the protooncogene CyclinD1 while upregulating the expression levels of tumor suppressor genes, P16 and P21 in MCF-7 and MDA-MB-231 cells. Furthermore, hMSCs from both sources also increased the expression levels of MYC, SNAI1, and TWIST, which promote the epithelial-mesenchymal transition and migration of breast cancer cells in both cell lines. The functional study suggests that the suppressive effect of CH-hMSCs and PL-hMSCs on MCF-7 and MDA-MB231 cell proliferation was mediated, at least in part, through IFN-γ. Conclusions. Our study suggests that CH-hMSCs and PL-hMSCs inhibited breast cancer cell proliferation by negatively regulating CYCLIND1 expression and upregulating the expression of the P16 and P21 genes. In contrast, hMSCs from both sources enhanced breast cancer cell migration, possibly by increasing the expression of MYC, SNAI1, and TWIST genes in those cells.

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

“…DPSC promoted the proliferation and metastasis of PC-3 cancer cells under in vitro co-culture conditions [ 36 ]. However, DPSC-conditioned medium had significant apoptotic and growth inhibitory effects on CRC cells through the MAPKinase and apoptotic signaling pathways [ 37 ]; and human MSCs derived from the placenta and the chorionic villus inhibited proliferation and enhanced migration of human breast cancer cells [ 38 ]. MSCs may have two conflicting effects on different types of tumor cells, either promoting or inhibiting them.…”

PL-hMSC and CH-hMSC derived soluble factors inhibit proliferation but improve hGBM cell migration by activating TGF-β and inhibiting Wnt signaling

“…As described in our previous study [ 23 ], placenta and chorion were separated from each other, cut into small pieces, and incubated for 30 min at 37°C in 0.25 percent (w/v) trypsin-EDTA (Thermo Fisher Scientific, U.S.A.). After being washed twice with PBS, digested tissues were resuspended in DMEM + 10% (v/v) Fetal Bovine Serum (FBS) (Thermo Fisher Scientific, U.S.A.) and cultured in 25 cm 2 flasks (Corning, U.S.A.) at 37°C in a humidified environment containing 5% CO 2 .…”

“…As described in our previous study [ 23 ], approximately 4 × 10 5 hMSCs (passage 3–5th) were resuspended in 50 μl PBS and treated with 10 μl of the following fluorochrome-labeled mouse anti-human monoclonal antibodies for 30 min at 4°C in the dark: anti-CD45-FITC (BD Pharmingen, U.S.A.), anti-CD34-PE (Biolegend, U.S.A.), anti-CD90-FITC (AbD Serotec, U.S.A.), and anti-CD73-PE (Biolegend, U.S.A.). Cells were then washed twice with PBS before being fixed with 1% (w/v) paraformaldehyde in PBS (Sigma-Aldrich, U.S.A.).…”

“…As described in our previous study [ 23 ], hMSCs (passage 3–5th) were seeded in a 6-well plate (Corning, U.S.A.) at a density of 4.5 × 10 3 cells/cm 2 and cultured in DMEM + 10% (v/v) FBS until their confluence reached 80%. For osteogenic differentiation, the medium was replaced with osteogenic differentiation medium [DMEM supplemented with 100 nM dexamethasone (Sigma-Aldrich, U.S.A.), 10 mM β-glycerophosphate (Sigma-Aldrich, U.S.A.), and 50 µg/ml ascorbic acid (Sigma-Aldrich, U.S.A.)].…”

“…As described in our previous study [ 23 ], to evaluate the effect of hMSC-derived soluble factors on GBM cell proliferation, U251 cells were seeded in a 96-well plate [SPL Life Science, Korea] at a density of 1 × 10 3 cells/well in DMEM + 10% (v/v) FBS and cultured for 12 h. At this stage, the cells were separated into three groups. In the first group (CH-CM), the medium was replaced with 10%, 25%, 50% or 75% (v/v) CH-hMSC-CMs in DMEM + 10% (v/v) FBS.…”