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

Nazneen Aslam; Elham Abusharieh; Duaa Abuarqoub; Dema Ali; Dana Majed Alhattab; Suha Wehaibi; Ban Al-Kurdi; Fatima Jamali; Walhan Alshaer; Hanan Jafar; Abdalla S. Awidi

doi:10.1016/j.omto.2020.11.005

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

Nazneen Aslam, Elham Abusharieh, Duaa Abuarqoub, Dema Ali, Dana Majed Alhattab, Suha Wehaibi, Ban Al-Kurdi, Fatima Jamali, Walhan Alshaer, Hanan Jafar, Abdalla S. Awidi

Biological, Environmental Sciences and Engineering

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	147-165
Number of pages	19
Journal	Molecular Therapy - Oncolytics
Volume	20
DOIs	https://doi.org/10.1016/j.omto.2020.11.005
State	Published - Nov 26 2020

Bibliographical note

KAUST Repository Item: Exported on 2021-02-05
Acknowledgements: 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.

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10.1016/j.omto.2020.11.005

https://repository.kaust.edu.sa/bitstream/10754/667215/1/1-s2.0-S2372770520301704-main.pdf

Cite this

Aslam, N., Abusharieh, E., Abuarqoub, D., Ali, D., Alhattab, D. M., Wehaibi, S., Al-Kurdi, B., Jamali, F., Alshaer, W., Jafar, H., & Awidi, A. S. (2020). 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. https://doi.org/10.1016/j.omto.2020.11.005

@article{d3601ffef40c4996bb7151c79d9c0047,

title = "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.",

author = "Nazneen Aslam and Elham Abusharieh and Duaa Abuarqoub and Dema Ali and Alhattab, {Dana Majed} and Suha Wehaibi and Ban Al-Kurdi and Fatima Jamali and Walhan Alshaer and Hanan Jafar and Awidi, {Abdalla S.}",

note = "KAUST Repository Item: Exported on 2021-02-05 Acknowledgements: 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.",

year = "2020",

month = nov,

day = "26",

doi = "10.1016/j.omto.2020.11.005",

language = "English (US)",

volume = "20",

pages = "147--165",

journal = "Molecular Therapy - Oncolytics",

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Aslam, N, Abusharieh, E, Abuarqoub, D, Ali, D, Alhattab, DM, Wehaibi, S, Al-Kurdi, B, Jamali, F, Alshaer, W, Jafar, H & Awidi, AS 2020, '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, vol. 20, pp. 147-165. https://doi.org/10.1016/j.omto.2020.11.005

TY - JOUR

T1 - Anti-oncogenic activities exhibited by paracrine factors of MSCs can be mediated by modulation of KITLG and DKK1 genes in glioma SCs in vitro

AU - Aslam, Nazneen

AU - Abusharieh, Elham

AU - Abuarqoub, Duaa

AU - Ali, Dema

AU - Alhattab, Dana Majed

AU - Wehaibi, Suha

AU - Al-Kurdi, Ban

AU - Jamali, Fatima

AU - Alshaer, Walhan

AU - Jafar, Hanan

AU - Awidi, Abdalla S.

N1 - KAUST Repository Item: Exported on 2021-02-05 Acknowledgements: 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.

PY - 2020/11/26

Y1 - 2020/11/26

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10754/667215

UR - https://linkinghub.elsevier.com/retrieve/pii/S2372770520301704

UR - http://www.scopus.com/inward/record.url?scp=85099961080&partnerID=8YFLogxK

U2 - 10.1016/j.omto.2020.11.005

DO - 10.1016/j.omto.2020.11.005

M3 - Article

C2 - 33575478

SN - 2372-7705

VL - 20

SP - 147

EP - 165

JO - Molecular Therapy - Oncolytics

JF - Molecular Therapy - Oncolytics

ER -

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

Bibliographical note

UN SDGs

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