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.
Highlights
Ovarian cancer is the lethal of all gynecologic malignancies
Our results showed a significant decrease in the level of CD24 when OVCAR3, CAOV3, IGROV3 and SKOV3 were co-cultured with BMMSC, umbilical cord derived MSCs (UCMSCs) and ADMSC and Conditioned media (CM)-Mesenchymal stem cells (MSCs). (p < 0.0001) (Fig. 3a, b, c, d)
We found by flow cytometry analysis that CD24 was significantly decreased when cocultured with MSCs and MSC-CM the results was more significant with CM of MSCs, this is consistent with the latest theory stating that the therapeutic effects of MSCs are due to their paracrine effects and not due to their differentiation capacity [45,46,47]
Summary
Ovarian cancer is the lethal of all gynecologic malignancies. Expected projections in 2018 estimate approximately 22,240 new diagnoses and 14,070 female deaths in the United States alone [1]. Mortality in ovarian cancer is predominantly due to tumor recurrence and acquired chemoresistance [2,3,4]. Tumor recurrence is common because majority of people are diagnosed at advanced stages of the disease [5, 6]. Ovarian carcinosarcomas were often treated with the same first-line chemotherapy as uterine carcinosarcomas, ifosfamide/paclitaxel [7,8,9,10,11]. Several single institution studies have provided convincing evidence that ovarian carcinosarcoma patients have lower response rates to chemotherapy and poor overall and disease-specific survival [14, 15]. The preferred first-line treatment for ovarian carcinosarcoma patients remains debatable [16,17,18]
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