Crosstalk between glial and glioblastoma cells triggers the “go-or-grow” phenotype of tumor cells

Cell Communication and Signaling

Research

Bruno Manadas¹  Sandra I. Anjo²  António J. Salgado³  Bruno M. Costa³  Ana Isabel Oliveira³  Sofia C. Serra³  Joana Vieira de Castro³ 

[1]CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal

[2]CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal

[3]Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal

[4]Life and Health Sciences Research Institute (ICVS), School of Medicine, Campus de Gualtar, University of Minho, 4710-057, Braga, Portugal

[5]ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Campus de Gualtar, University of Minho, 4710-057, Braga, Portugal

关键词: Glioblastoma;    Glial cells;    Tumor microenvironment;    Secretome;    Paracrine effect;   

DOI  :  10.1186/s12964-017-0194-x

 received in 2017-05-30, accepted in 2017-09-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundGlioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells.MethodsConditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways.ResultsThe proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation.ConclusionsTogether, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells.

【 授权许可】

CC BY   
© The Author(s). 2017