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

• Published in: Molecular therapy. Oncolytics Vol. 20; pp. 147 - 165
• Main Authors: Aslam, Nazneen, Abusharieh, Elham, Abuarqoub, Duaa, Ali, Dema, Al-Hattab, Dana, Wehaibi, Suha, Al-Kurdi, Ban, Jamali, Fatima, Alshaer, Walhan, Jafar, Hanan, Awidi, Abdalla S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: BM-MSCs; conditioned media; CSC arrays; glioma stem cells; gliospheres; mesenchymal stem cells; microarray; Original; signaling pathways; stemness; WJ-MSCs; microarray; gliospheres; WJ-MSCs; signaling pathways; mesenchymal stem cells; BM-MSCs; CSC arrays; stemness; conditioned media; glioma stem cells
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2020.11.005

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. [Display omitted] Glioblastoma has limited treatment options due to the selective blood-brain barrier. Paracrine factors from mesenchymal stem cells can cross this barrier and exhibited anti-oncogenic potential for glioma stem cells in vitro. These soluble factors can be a tool as a combinatorial therapy for the treatment of glioblastomas.