The low affinity A2B adenosine receptor enhances migratory and invasive capacity in vitro and angiogenesis in vivo of glioblastoma stem-like cells.
Autor: Erices, José I.; Niechi, Ignacio; Uribe-Ojeda, Atenea; Toro, Mª Ángeles; García Romero, Noemí; Carrión Navarro, Josefa; Monago Sánchez, Álvaro; Ayuso Sacido, Ángel; San Martín, Rody; Quezada-Monras, Claudia
Resumen: Glioblastoma (GBM) is the most common and deadlymalignant brain tumor,with
a median survival of 15 to 17 months for a patient. GBM contains a cellular
subpopulation known as GBM stem-like cells (GSCs) that persist in hypoxic
niches and are capable of infiltrating into healthy brain tissue. For this reason,
GSCs are considered one of the main culprits for GBM recurrence. A hypoxic
microenvironment increases extracellular adenosine levels, activating the low
affinity A2B adenosine receptor (A2BAR). Adenosine, through A2BAR, is capable of
modulating invasiveness. However, its role in the invasion/migration of hypoxic-
GSCs is still unknown. This study aims to understand the importance of A2BAR in
modulating themigratory/invasive capacity of GSCs under hypoxia. Data analysis
from The Cancer Genome Atlas (TCGA) program correlates A2BAR expression
with high-grade glioma and hypoxic necrotic areas. U87MG and primary culturederived
GSCs under hypoxic conditions (0.5% O2) increased A2BAR mRNA and
protein levels. As expected, the migratory and invasive capacity of GSCs
increased under hypoxia, which was counteracted by blocking A2BAR, through
the downregulation of MMP9 activity and epithelial–mesenchymal transition
marker expression. Finally, in a xenograft mouse model, we demonstrate that
treatment with MRS1754 did not affect the tumor volume but could decrease
blood vessel formation and VEGF expression. Our results suggest that
extracellular adenosine, through the activation of A2BAR, enhances the
migratory and invasive capacity of GSCs in vitro under hypoxic conditions.
Targeting A2BAR can be an effective therapy for GBM recurrence.
Identificador universal: https://hdl.handle.net/10641/3336
Fecha: 2022
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