Anti-proliferative effects of mesenchymal stem cells (MSCs) derived from multiple sources on ovarian cancer cell lines: an in-vitro experimental study

Abstract

Mesenchymal stem cells (MSCs) have surfaced as ideal candidates for treatment of different therapeutically challenging diseases however their effect on cancer cells is not well determined. In this study, we investigated the effect of MSCs derived from human bone marrow (BM), adipose tissue (AT), and umbilical cord derived MSCs (UC-MSCs) on ovarian cancer. Measurements of ovarian tumor marker proteins were computed by ELISA. Proliferative, apoptosis and anti-inflammatory effects of the MSCs were measured by Flow cytometry (FCM). MMPs expression was measured by RT-PCR. The co-culture of cancer cell lines OVCAR3, CAOV3, IGROV3 and SKOV3 with the conditioned media of MSCs (CM-MSC) and MSCs showed an increase in cellular apoptosis, along with a reduction in the level of CA-125 and a decline of LDH and beta-hCG. A decrease in CD24 of the cancer cell lines in co-culture with the CM-MSCs showed a reduction of the cancer tumorigenicity. In addition, the invasion and aggressiveness of cancer cell lines was significantly decreased by CM-MSC; this was translated by a decrease in MMP-2, MMP-9, and CA-125 mRNA expression, and an increase in TIMP 1, 2, and 3 mRNA expression. An increase in IL-4 and IL-10 cytokines, and a decrease in GM-CSF, IL-6, and IL-9, were also noted. In conclusion, mesenchymal stem cells derived from different sources and their conditioned media appear to have a major role in inhibition of cancer aggressiveness and might be considered as a potential therapeutic tool in ovarian cancer.

Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

“…In an experiment on breast cancer, MSCs were demonstrated to suppress cancer cell growth and sensitize the cancer cells to radiotherapy through inhibiting the STAT3 signaling pathway ( 26 ). Moreover, MSCs and their conditioned media also have a major role in anti-proliferation of ovarian cancer cells and can be considered as a potential therapeutic tool in ovarian cancer ( 27 ).…”

Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles

“…These results suggest that HATMSC2-MVs at a ratio of 100:1 induce mechanisms governing ovarian cancer cell death via both apoptosis and necrosis. Studies on the anti-cancer properties of the MSC secretome report that co-culture of MSCs of different tissue origin with ovarian cancer cell lines increases apoptosis with varying effects [21]. Interestingly, the percentage of apoptotic cells was higher when the supernatant derived from AT-MSCs was applied compared to the supernatants derived from BM-MSCs and UC-MSCs [21].…”

DEAD-Box Helicase 4 (Ddx4)+ Stem Cells Sustain Tumor Progression in Non-Serous Ovarian Cancers

“…In this regard, the cross-talk between mesenchymal and tumor cells has been shown to induce transcriptomic changes in the latter, characterized by the upregulation of genes involved in cell proliferation, migration and invasiveness that ultimately lead to the acquisition of a pro-metastatic phenotype [ 49 ]. On the other hand, Khalil and co-workers demonstrated that MSCs from different sources were capable to exert a pro-apoptotic effect in vitro on several OC lines, while decreasing tumor cell invasiveness and aggressiveness [ 52 ]. In our experimental model, by co-culturing A2780 with tumor-derived ML-Ddx4 + cells, we observed that the latter did not compromise OC cell viability, but preserved their proliferation rate, as confirmed by the transcriptomic variations that we observed in subsequent experimental steps.…”