Cargando…

Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology

BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodifi...

Descripción completa

Detalles Bibliográficos
Autores principales: Vieira de Castro, Joana, Gomes, Eduardo D., Granja, Sara, Anjo, Sandra I., Baltazar, Fátima, Manadas, Bruno, Salgado, António J., Costa, Bruno M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625623/
https://www.ncbi.nlm.nih.gov/pubmed/28969635
http://dx.doi.org/10.1186/s12967-017-1303-8
_version_ 1783268416625311744
author Vieira de Castro, Joana
Gomes, Eduardo D.
Granja, Sara
Anjo, Sandra I.
Baltazar, Fátima
Manadas, Bruno
Salgado, António J.
Costa, Bruno M.
author_facet Vieira de Castro, Joana
Gomes, Eduardo D.
Granja, Sara
Anjo, Sandra I.
Baltazar, Fátima
Manadas, Bruno
Salgado, António J.
Costa, Bruno M.
author_sort Vieira de Castro, Joana
collection PubMed
description BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression. Considering that one of the major mechanisms by which MSCs interact with and modulate tumor cells is via secreted factors, we studied how the secretome of MSCs modulates critical hallmark features of GBM cells. METHODS: The effect of conditioned media (CM) from human umbilical cord perivascular cells (HUCPVCs, a MSC population present in the Wharton’s jelly of the umbilical cord) on GBM cell viability, migration, proliferation and sensitivity to temozolomide treatment of U251 and SNB-19 GBM cells was evaluated. The in vivo chicken chorioallantoic membrane (CAM) assay was used to evaluate the effect of HUCPVCs CM on tumor growth and angiogenesis. The secretome of HUCPVCs was characterized by proteomic analyses. RESULTS: We found that both tested GBM cell lines exposed to HUCPVCs CM presented significantly higher cellular viability, proliferation and migration. In contrast, resistance of GBM cells to temozolomide chemotherapy was not significantly affected by HUCPVCs CM. In the in vivo CAM assay, CM from HUCPVCs promoted U251 and SNB-19 tumor cells growth. Proteomic analysis to characterize the secretome of HUCPVCs identified several proteins involved in promotion of cell survival, proliferation and migration, revealing novel putative molecular mediators for the effects observed in GBM cells exposed to HUCPVCs CM. CONCLUSIONS: These findings provide novel insights to better understand the interplay between GBM cells and MSCs, raising awareness to potential safety issues regarding the use of MSCs as stem-cell based therapies for GBM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1303-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5625623
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-56256232017-10-12 Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology Vieira de Castro, Joana Gomes, Eduardo D. Granja, Sara Anjo, Sandra I. Baltazar, Fátima Manadas, Bruno Salgado, António J. Costa, Bruno M. J Transl Med Research BACKGROUND: Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression. Considering that one of the major mechanisms by which MSCs interact with and modulate tumor cells is via secreted factors, we studied how the secretome of MSCs modulates critical hallmark features of GBM cells. METHODS: The effect of conditioned media (CM) from human umbilical cord perivascular cells (HUCPVCs, a MSC population present in the Wharton’s jelly of the umbilical cord) on GBM cell viability, migration, proliferation and sensitivity to temozolomide treatment of U251 and SNB-19 GBM cells was evaluated. The in vivo chicken chorioallantoic membrane (CAM) assay was used to evaluate the effect of HUCPVCs CM on tumor growth and angiogenesis. The secretome of HUCPVCs was characterized by proteomic analyses. RESULTS: We found that both tested GBM cell lines exposed to HUCPVCs CM presented significantly higher cellular viability, proliferation and migration. In contrast, resistance of GBM cells to temozolomide chemotherapy was not significantly affected by HUCPVCs CM. In the in vivo CAM assay, CM from HUCPVCs promoted U251 and SNB-19 tumor cells growth. Proteomic analysis to characterize the secretome of HUCPVCs identified several proteins involved in promotion of cell survival, proliferation and migration, revealing novel putative molecular mediators for the effects observed in GBM cells exposed to HUCPVCs CM. CONCLUSIONS: These findings provide novel insights to better understand the interplay between GBM cells and MSCs, raising awareness to potential safety issues regarding the use of MSCs as stem-cell based therapies for GBM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1303-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-02 /pmc/articles/PMC5625623/ /pubmed/28969635 http://dx.doi.org/10.1186/s12967-017-1303-8 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Vieira de Castro, Joana
Gomes, Eduardo D.
Granja, Sara
Anjo, Sandra I.
Baltazar, Fátima
Manadas, Bruno
Salgado, António J.
Costa, Bruno M.
Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title_full Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title_fullStr Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title_full_unstemmed Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title_short Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
title_sort impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625623/
https://www.ncbi.nlm.nih.gov/pubmed/28969635
http://dx.doi.org/10.1186/s12967-017-1303-8
work_keys_str_mv AT vieiradecastrojoana impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT gomeseduardod impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT granjasara impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT anjosandrai impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT baltazarfatima impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT manadasbruno impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT salgadoantonioj impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology
AT costabrunom impactofmesenchymalstemcellssecretomeonglioblastomapathophysiology