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GBM-Derived Wnt3a Induces M2-Like Phenotype in Microglial Cells Through Wnt/β-Catenin Signaling

Overview of attention for article published in Molecular Neurobiology, June 2018
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Title
GBM-Derived Wnt3a Induces M2-Like Phenotype in Microglial Cells Through Wnt/β-Catenin Signaling
Published in
Molecular Neurobiology, June 2018
DOI 10.1007/s12035-018-1150-5
Pubmed ID
Authors

Diana Matias, Luiz Gustavo Dubois, Bruno Pontes, Luciane Rosário, Valeria Pereira Ferrer, Joana Balça-Silva, Anna Carolina Carvalho Fonseca, Lucy Wanjiku Macharia, Luciana Romão, Tania Cristina Leite de Sampaio e Spohr, Leila Chimelli, Paulo Niemeyer Filho, Maria Celeste Lopes, José Garcia Abreu, Flavia Regina Souza Lima, Vivaldo Moura-Neto

Abstract

Glioblastoma is an extremely aggressive and deadly brain tumor known for its striking cellular heterogeneity and capability to communicate with microenvironment components, such as microglia. Microglia-glioblastoma interaction contributes to an increase in tumor invasiveness, and Wnt signaling pathway is one of the main cascades related to tumor progression through changes in cell migration and invasion. However, very little is known about the role of canonical Wnt signaling during microglia-glioblastoma crosstalk. Here, we show for the first time that Wnt3a is one of the factors that regulate interactions between microglia and glioblastoma cells. Wnt3a activates the Wnt/β-catenin signaling of both glioblastoma and microglial cells. Glioblastoma-conditioned medium not only induces nuclear translocation of microglial β-catenin but also increases microglia viability and proliferation as well as Wnt3a, cyclin-D1, and c-myc expression. Moreover, glioblastoma-derived Wnt3a increases microglial ARG-1 and STI1 expression, followed by an upregulation of IL-10 mRNA levels, and a decrease in IL1β gene expression. The presence of Wnt3a in microglia-glioblastoma co-cultures increases the formation of membrane nanotubes accompanied by changes in migration capability. In vivo, tumors formed from Wnt3a-stimulated glioblastoma cells presented greater microglial infiltration and more aggressive characteristics such as growth rate than untreated tumors. Thus, we propose that Wnt3a belongs to the arsenal of factors capable of stimulating the induction of M2-like phenotype on microglial cells, which contributes to the poor prognostic of glioblastoma, reinforcing that Wnt/β-catenin pathway can be a potential therapeutic target to attenuate glioblastoma progression.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 15%
Student > Bachelor 5 12%
Student > Master 5 12%
Researcher 5 12%
Professor 5 12%
Other 5 12%
Unknown 10 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 27%
Medicine and Dentistry 6 15%
Neuroscience 5 12%
Agricultural and Biological Sciences 3 7%
Pharmacology, Toxicology and Pharmaceutical Science 1 2%
Other 2 5%
Unknown 13 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 July 2018.
All research outputs
#20,525,274
of 23,094,276 outputs
Outputs from Molecular Neurobiology
#2,828
of 3,498 outputs
Outputs of similar age
#288,118
of 328,571 outputs
Outputs of similar age from Molecular Neurobiology
#102
of 122 outputs
Altmetric has tracked 23,094,276 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,498 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,571 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 122 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.