Anti-oncogenic activities exhibited by paracrine factors of MSCs can be mediated by modulation of KITLG and DKK1 genes in glioma SCs in vitro
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ArticleAuthors
Aslam, Nazneen
Abusharieh, Elham
Abuarqoub, Duaa
Ali, Dema
Alhattab, Dana Majed

Wehaibi, Suha
Al-Kurdi, Ban
Jamali, Fatima
Alshaer, Walhan
Jafar, Hanan
Awidi, Abdalla S.
Date
2020-11-26Submitted Date
2020-08-04Permanent link to this record
http://hdl.handle.net/10754/667215
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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.Citation
Aslam, N., Abusharieh, E., Abuarqoub, D., Ali, D., Al-Hattab, D., Wehaibi, S., … Awidi, A. S. (2021). Anti-oncogenic activities exhibited by paracrine factors of MSCs can be mediated by modulation of KITLG and DKK1 genes in glioma SCs in vitro. Molecular Therapy - Oncolytics, 20, 147–165. doi:10.1016/j.omto.2020.11.005Sponsors
We are thankful to all the participants and management team at the Cell Therapy Center for their continuous cooperation and funding support for this study. We extend our gratitude to Dr Noor Gammoh from the University of Edinburgh, whose valuable comments make the manuscript clear and presentable. The graphical abstract was created with BioRender (https://biorender.com/). Conceptualization and Design, N.A.; Methodology, N.A. and E.A.; Formal Analysis, N.A. and D.A.; Investigation, N.A. E.A. D. Ali, S.W. and B.A.; Resources, D.A.-H. ; Data Curation, W.A.; Writing – Original Draft, N.A.; Writing – Review & Editing, F.J.; Project Administration, H.J. and A.A.; Funding Acquisition, A.A. The authors declare no competing interests.Publisher
Elsevier BVJournal
Molecular Therapy - OncolyticsAdditional Links
https://linkinghub.elsevier.com/retrieve/pii/S2372770520301704ae974a485f413a2113503eed53cd6c53
10.1016/j.omto.2020.11.005
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