Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Campus Capão do Leão S/N Caixa Postal 354, Pelotas, CEP 96010900, RS, Brazil.
Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, 245 Rua Sarmento Leite, Porto Alegre, CEP 90050-170, RS, Brazil.
Adv Exp Med Biol. 2020;1202:87-108. doi: 10.1007/978-3-030-30651-9_5.
Among the pathological alterations that give tumor cells invasive potential, purinergic signaling is emerging as an important component. Studies performed in in vitro, in vivo and ex vivo glioma models indicate that alterations in the purinergic signaling are involved in the progression of these tumors. Gliomas have low expression of all E-NTPDases, when compared to astrocytes in culture. Nucleotides induce glioma proliferation and ATP, although potentially neurotoxic, does not evoke cytotoxic action on the majority of glioma cells in culture. The importance of extracellular ATP for glioma pathobiology was confirmed by the reduction in glioma tumor size by apyrase, which degrades extracellular ATP to AMP, and the striking increase in tumor size by over-expression of an ecto-enzyme that degrades ATP to ADP, suggesting the effect of extracellular ATP on the tumor growth depends on the nucleotide produced by its degradation. The participation of purinergic receptors on glioma progression, particularly P2X, is involved in the resistance to ATP-induced cell death. Although more studies are necessary, the purinergic signaling, including ectonucleotidases and receptors, may be considered as future target for glioma pharmacological or gene therapy.
在赋予肿瘤细胞侵袭潜力的病理改变中，嘌呤能信号转导正在成为一个重要组成部分。在体外、体内和离体神经胶质瘤模型中进行的研究表明，嘌呤能信号转导的改变参与了这些肿瘤的进展。与培养中的星形胶质细胞相比，神经胶质瘤中所有 E-NTPDases 的表达都较低。核苷酸诱导神经胶质瘤增殖，尽管 ATP 具有潜在的神经毒性，但在培养中的大多数神经胶质瘤细胞中不会引起细胞毒性作用。通过将细胞外 ATP 降解为 AMP 的脱氨酶（apyrase）降低神经胶质瘤肿瘤大小，以及通过过表达将 ATP 降解为 ADP 的外切酶显著增加肿瘤大小，证实了细胞外 ATP 对神经胶质瘤病理生物学的重要性，这表明细胞外 ATP 对肿瘤生长的影响取决于其降解产生的核苷酸。嘌呤能受体参与神经胶质瘤的进展，特别是 P2X 受体，与对 ATP 诱导的细胞死亡的抵抗有关。尽管还需要更多的研究，但嘌呤能信号转导，包括外核苷酸酶和受体，可能被认为是神经胶质瘤药理学或基因治疗的未来靶点。
