Cytokines secreted by human Wharton's jelly stem cells inhibit the proliferation of ovarian cancer (OVCAR3) cells in�vitro

Abstract

Cytokines enhance tumour cell recognition via cytotoxic effector cells and are therefore effectively used in cancer immunotherapy. Mesenchymal stem cells have efficient homing potential and have been used to target and inhibit various types of cancer mediated by the release of soluble/bioactive factors. Initial evaluation of the human Wharton's jelly stem cell conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against an ovarian cancer cell line (OVCAR3) demonstrated their inhibitory effect in vitro . The secreted cytokine profile was then studied to understand whether the OVCAR3 inhibitory effect was mediated by the cytokines. Expression of cytokines in OVCAR3 following 48 h treatment with hWJSC extracts, namely the hWJSC-CM (50%) and hWJSC-CL (10 µg/ml), was evaluated using multiplex cytokine assay. Paclitaxel (5 nM) was used as a positive control. Cytokines tumour necrosis factor α, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-13, IL-17, IL-1β and granulocyte colony-stimulating factor, reported to be involved in tumour growth, invasion and migration, were significantly decreased. Cytokines with antitumour effects, namely IL-1 receptor antagonist (IL-1RA), IL-2, IL-2 receptor, IL-5, IL-7, IL-12, IL-15, interferon (IFN)-α and IFN-γ, were mildly increased or decreased. Only the increases in IL-1RA (with paclitaxel, hWJSC-CM and hWJSC-CL) and granulocyte-macrophage colony-stimulating factor (with hWJSC-CL) were statistically significant. The chemokines monocyte chemoattractant protein 1, macrophage inflammatory protein (MIP)-1α, MIP-1β and Regulated Upon Activation, Normally T-Expressed, and Secreted were significantly decreased while monokine induced by IFN-γ, IFN-γ induced protein 10 and Eotaxin demonstrated mild decreases. The growth factors basic fibroblast growth factor, vascular endothelial growth factor and hepatocyte growth factor were significantly decreased. Heatmaps demonstrated differential fold changes in cytokines and hierarchical cluster analysis revealed 3 major and 7 minor sub-clusters of associated cytokines, chemokines and growth factors. In conclusion, the hWJSC extracts decreased the expression of oncogenic cytokines, chemokines and growth factors, which mediated the inhibition of OVCAR3 cells in vitro .

Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

“…We did not detect IFN-γ, FGF-2, GM-CSF, IL-17A, IL-2, MIP-1α, TGF-β3 in any MSC supernatant and this observation is in agreement with previous published results [ 91 , 92 ]. In the case of G-CSF, IFNα, PDGF AA our analysis shows their low concentrations in supernatants, which stays in line with other reports.…”

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

“…New treatment modalities, including novel agents and small molecule inhibitors, are currently under investigation. Remotely, mesenchymal stem cells (MSCs) and their soluble factors are reported to exhibit bene cial anticancer effects (49,50,51). In order to investigate further if the soluble factors of MSCs may affect different pathways related to proliferation and stemness of GSC to transform them into non-stem-like cells prone to therapies, we planned this study.…”

Suppression of Ovarian Cancer Cell Growth by AT-MSC Microvesicles

“…The HATMSC2-MVs used in this study affect both histologically different cell lines, the ES-2 cells and the OAW-42 cells, by increasing the production of tumor-suppressive cytokines, such as IL-1ra, IL-2, IL-2Ra, IL-12-p40, IL12-p70, IL-15, and IFN-γ. Studies that used bioactive factors released to the culture medium from Wharton's jelly MSCs led to a similar inhibition of the proliferation of the ovarian cancer cell line OVCAR3 through a decreased expression of oncogenic cytokines and growth factors and an increased expression of anti-tumor related cytokines [35]. The anti-inflammatory properties of IL-1ra, a naturally occurring inhibitor to IL-1, contribute to tumor growth inhibition by competitive binding to IL-1 receptors blocking cancer-promoting activity of IL-1 [36].…”