Title:Chemoresistance in High-Grade Gliomas: Relevance of Adenosine Signalling in Stem-Like Cells of Glioblastoma Multiforme
Volume: 15
Issue: 10
Author(s): Wallys Garrido, Jose Dellis Rocha, Catherinne Jaramillo, Katia Fernandez, Carlos Oyarzun, Rody San Martin and Claudia Quezada
Affiliation:
关键词:
腺苷，腺苷A3受体，多形性恶性胶质瘤，恶性胶质瘤干细胞样细胞，与蛋白-1（Mrp1）转运体相关的多药物抗性
摘要: Glioblastoma multiforme (GBM) is the most common glial cell-derived brain tumour, with one of the worst
prognoses among all cancers. GBM cells are infiltrative and extremely resistant to radio- and chemotherapy, which inevitably
leads to recurrence after surgical resection. These inherent GBM properties are the reasons that patient treatment has
not seen major improvements in decades. Studies have consistently shown that glioblastoma stem-like cells (GSCs) are
responsible for the tumourigenic properties in the GBM population. In fact, their self-renewal and proliferative potential
are required for tumour growth, and their extreme chemoresistance leads to early recurrence of this tumour. Among those
mechanisms associated with chemoresistance and having the greatest clinical impact in cancer treatment, are the activities
of plasma membrane transporters that extrude antitumour drugs from the cell, thus notably decreasing the pharmacological
efficiency of these drugs. The multiple drug resistance associated protein-1 (Mrp1) transporter has been shown to be
particularly important in GBM, as inhibition of Mrp1 activity notably chemosensitises cells to antiproliferative drugs. As
current therapeutic options for GBM offer only a poor improvement in overall survival rate, alternative strategies for
overcoming tumour resistance are urgently sought after. To this end, it is of major clinical relevance to know more about
the endogenous modulators that control Mrp1 expression within the pathological environment of the tumour. This review
describes the particular properties of glioblastoma cells that overcome multimodal therapy and relapse, with an emphasis
on the microenvironmental tumour properties that influence the chemoresistance phenotype to antiproliferative drugs. We
also discuss alternative methods of reversal of Mrp1-mediated chemoresistance in these cells by targeting extracellular
adenosine production or signalling through particular plasma membrane receptors.
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