Abstract
Glioblastoma is the brain tumor with the worst prognosis. This is mainly due to a cell subpopulation with an extremely aggressive potential, called glioblastoma stem-like cells (GSCs). These cells produce high levels of extracellular adenosine, which are increased even more under hypoxic conditions. Under hypoxia, adenosine signaling is related to HIF-2α expression, enhancing cell aggressiveness. Adenosine can be degraded using recombinant adenosine deaminase (ADA) to revert its pathological effects. The aim of this study was to degrade adenosine using ADA in order to decrease malignancy of GSCs. Adenosine depletion was performed using recombinant ADA. Migration and invasion were measured by transwell and matrigel-coated transwell assay, respectively. HIF-2α-dependent cell migration/invasion decreased in GSCs treated with ADA under hypoxia. MRPs-mediated chemoresistance and colony formation decreased in treatment with ADA. In conclusion, adenosine depletion using adenosine deaminase decreases GSCs aggressiveness.
Highlights
Glioblastoma (GBM) is the most common and aggressive brain tumor with enhanced proliferation, chemoresistance and invasive potential [1,2,3]
Adenosine, glioblastoma stem-like cells (GSCs) derived from U87MG cell line (U87-GSCs) were incubated with recombinant adenosine deaminase (ADA)
Our group had previously reported that adenosine levels are elevated in GSCs and are further increased under hypoxic conditions [41]
Summary
Glioblastoma (GBM) is the most common and aggressive brain tumor with enhanced proliferation, chemoresistance and invasive potential [1,2,3]. Despite the multimodal treatments including tumor resection followed by radiotherapy and chemotherapy [2,4,5], there has been no improvement in the survival rates, due to the early and inevitable tumor recurrence [6,7,8]. Recurrence is mediated mainly by a cellular subpopulation with stem cells characteristics called glioblastoma stem-like cells (GSCs) [9]. These cells can be found in specific niches within the tumor, associated with blood vessels with an appropriate oxygen supply or under hypoxic regions associated with necrosis [10].
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