The low affinity A2B adenosine receptor enhances migratory and invasive capacity in vitro and angiogenesis in vivo of glioblastoma stem-like cells

• DOI: 10.3389/fonc.2022.969993
• Publication Date: 2022-08-18T06:30:55Z
• Authors: José I. Erices; Ignacio Niechi; Atenea Uribe-Ojeda; María de los Ánge...; Noemí García-Romero; Josefa Carrión-Na...; Álvaro Monago-Sán...; Ángel Ayuso-Sacido; Rody San Martin; Claudia Quezada-M...
• Keywords: Hypoxia

Glioblastoma (GBM) is the most common and deadly malignant brain tumor, with a median survival of 15 to 17 months for patient. GBM contains cellular subpopulation known as stem-like cells (GSCs) that persist in hypoxic niches are capable infiltrating into healthy tissue. For this reason, GSCs considered one main culprits recurrence. A microenvironment increases extracellular adenosine levels, activating low affinity A2B receptor (A2BAR). Adenosine, through A2BAR, modulating invasiveness. However, its role invasion/migration hypoxic-GSCs still unknown. This study aims understand importance A2BAR migratory/invasive capacity under hypoxia. Data analysis from The Cancer Genome Atlas (TCGA) program correlates expression high-grade glioma necrotic areas. U87MG primary culture-derived conditions (0.5% O2) increased mRNA protein levels. As expected, migratory invasive hypoxia, which was counteracted by blocking downregulation MMP9 activity epithelial-mesenchymal transition marker expression. Finally, xenograft mouse model, we demonstrate treatment MRS1754 did not affect tumor volume but could decrease blood vessel formation VEGF Our results suggest adenosine, activation enhances vitro conditions. Targeting can be an effective therapy