WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background.</jats:bold> Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Anti-tumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain beneficial effects However, different types of MSCs yielded different conflicting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study. <jats:bold>Methods</jats:bold>. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (BM-MSCs) were harvested and used as treatments on glioshperes (3D) to investigate the effect on proliferation, invasion and self renewal properties of GSCs. Microarray analysis was used to determine the effect at molecular level. Specific human CSC gene arrays were applied to validate the findings of the microarray explicitly the pluripotency of the GSCs. <jats:bold>Results.</jats:bold> Our results from functional and molecular assays showed that condition media (CM) from both types of MSCs inhibited the metabolism by interrupting oxidative phosphorylation, arrested the cell cycle, induced cell differentiation, targeted the pluripotency and up-regulated the immune response in GSCs. Moreover , condition media from both types of MSCs significantly affected the same genes (<jats:italic>KITLG</jats:italic> and <jats:italic>DKK1</jats:italic>) causing a similar effect while using slightly different routes and signaling pathways signifying their individual effects.<jats:bold>Conclusion.</jats:bold>We conclude that mesenchymal stem cells possess antitumor properties and paracrine factors of mesenchymal stem cells in combination with anti-immune modalities can provide novel therapeutic targets for glioma treatment.</jats:p>

Identification and characterization of four immune-related signatures in keloid

“…DKK1 is an inhibitor of the Wnt signaling pathway, which can regulate Wnt through negative feedback and participates in tumor cell proliferation, apoptosis, migration, and angiogenesis (92,93). DKK1 binds to the LRP6 co-receptor and inhibits b-catenin-dependent Wnt signaling, and the downregulation of b-catenin is crucial to human immune function (94,95). Furthermore, DKK1 can regulate immune cells and suppress immune reactions through the GSK3b/E2F1/ T-bet axis in CD8 + T cells (96,97).…”

Cell-based and cell-free immunotherapies for glioblastoma: current status and future directions

“…Yuzaburo Shimizu et al ( 77) conducted a prospective clinical experiment in which they discovered that bone marrow MSCs could be collected from GBM patients who had previously had chemotherapy and that bone marrow MSCs were efficient carriers of oncolytic virus. Additionally, Nazneen Aslam et al (78) suggested a possible solution for GSCs and discovered that when actively developing GSCs were treated with paracrine factors from MSCs, the prospective growth capacity and pluripotent of GSCs were disrupted. This effect was mediated by up regulation of the DKK1 gene, which in addition was mediated by up regulation of the Wnt pathway mediated by inhibition of growth factor activity and down regulation of the KITLG gene activated by growth factor and cytokine activity, thus exhibiting antitumor properties.…”