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.
Highlights
The modern theory of carcinogenesis focuses on the presence of malignant transformations in adult tissue stem cells.[1]
We found that gliosphere conditioned media (CM) (GSCM) harvested from BM1-mesenchymal stem cells (MSCs) showed statistically significant inhibition of proliferation of glioblastoma CSCs (GSCs) in any formulation of CM concerning both controls at 96 h (p < 0.01, p < 0.0001)
The inhibition was translated into decreased oncogenic activities, including stemness of GSCs through different pathways mediated by KITLG and DKK1 genes
Summary
The modern theory of carcinogenesis focuses on the presence of malignant transformations in adult tissue stem cells.[1]. The presence of CSCs has been reported in both hematologic malignancies and solid tumors (i.e., breast cancer, brain tumors, malignant melanoma, or prostate cancer).[12,13]
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