Impact of mesenchymal stem cells’ secretome on glioblastoma pathophysiology

Journal of Translational Medicine

Research

Bruno Manadas¹  Sandra I. Anjo²  Fátima Baltazar³  Eduardo D. Gomes³  António J. Salgado³  Bruno M. Costa³  Sara Granja³  Joana Vieira de Castro³ 

[1] CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal;CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal;Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3004-517, Coimbra, Portugal;Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal;ICVS/3B’s-PT Government Associate Laboratory, University of Minho, Braga/Guimarães, Campus de Gualtar, 4710-057, Braga, Portugal;

关键词: Glioblastoma;    Mesenchymal stem cells;    Human umbilical cord perivascular cells;    Conditioned media;    Secretome;    Viability;    Proliferation;    Migration;    Proteomics;   

DOI  :  10.1186/s12967-017-1303-8

 received in 2017-06-05, accepted in 2017-09-19,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundGlioblastoma (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.MethodsThe 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.ResultsWe 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.ConclusionsThese 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.

【 授权许可】

CC BY   
© The Author(s) 2017