Anti-oncogenic activities exhibited by paracrine factors of MSCs can be mediated by modulation of KITLG and DKK1 genes in glioma SCs in vitro

Abstract

Cancer stem cells (CSCs) use their stemness properties to perpetuate their lineage and survive chemotherapy. Currently cell-based and cell-free therapies are under investigation to develop novel anti-cancer treatment modalities. We designed this study to investigate how cell extracts of mesenchymal stem cells affect the growth of glioma stem cells in vitro . Gliospheres were generated from the U87MG cell line and treated with conditioned media of Wharton’s jelly and bone marrow mesenchymal stem cells. The effects were investigated at the functional and molecular levels. Our results showed that conditioned media from both types of mesenchymal stem cells changed the morphology of spheres and inhibited the proliferation, invasion, and self-renewal ability of glioma stem cells. At the molecular level, metabolism interruption at oxidative phosphorylation, cell cycle arrest, cell differentiation, and upregulation of the immune response were observed. Furthermore, this effect was mediated by the upregulation of the DKK1 gene inhibiting the Wnt pathway mediated by growth factor activity and downregulation of the KITLG gene activated by growth factor and cytokine activity, inhibiting multiple pathways. We conclude that different types of mesenchymal stem cells possess antitumor properties and their paracrine factors, in combination with anti-immune modalities, can provide practical therapeutic targets for glioblastoma treatment.

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 β-catenin-dependent Wnt signaling, and the downregulation of β-catenin is crucial to human immune function ( 94 , 95 ). Furthermore, DKK1 can regulate immune cells and suppress immune reactions through the GSK3β/E2F1/T-bet axis in CD8 + T cells ( 96 , 97 ).…”

KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect

“…These pathways are involved in the regulation of cell survival, differentiation, and proliferation [ 24 ]. Aberrant expression of KITLG by autocrine/paracrine stimulation mechanisms has been discovered in various cancers, such as colorectal cancer [ 31 ], non-small cell lung cancer [ 32 ], glioblastoma [ 33 ], and thymoma [ 34 ]. Our findings confirm that AGEs enhanced the expression and secretion of KITLG in HGECs, which, in turn, promoted EndoMT and increased the permeability of HGECs by an autocrine effect.…”

Mechanisms of analgesic effect of mesenchymal stem cells in osteoarthritis pain

“…In OA, high levels of Wnt are associated with progressive joint damage[ 84 ] and hyperalgesia[ 69 ]. Since MSCs were found to inhibit the Wnt/β-Catenin pathway in a number of disorders[ 85 , 86 ], this pathway could be involved in MSC analgesic mechanism and should be investigated further. In the study by Lee et al [ 63 ], administration of signal transducer and activator of transcription 3-inhibited MSCs reduced the levels of inflammatory mediators and chemokines in the OA joint, and this was associated with improvement in pain behavior and decreased TRPV1 expression in the dorsal root ganglion.…”