Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

IF 3 4区 医学 Q2 NEUROSCIENCES
Yong-Sheng Xu, Jun Xiang, Si-Jian Lin
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Abstract

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Abstract Image

P2X7 嘌呤能受体在癌症和癌症相关疼痛中的功能作用
大量研究表明,ATP 门控离子通道嘌呤能 2X7 受体(P2X7R)在肿瘤进展和癌痛发病机制中发挥着重要作用。P2X7R 需要细胞外 ATP 的激活才能发挥其调节作用。在肿瘤发生发展或癌症诱发疼痛的过程中,肿瘤细胞或肿瘤微环境中的其他细胞(如肿瘤相关免疫细胞)会释放出 ATP,从而激活 P2X7R,打开细胞膜上的离子通道,影响细胞内分子代谢,调节肿瘤细胞的活性。此外,在肿瘤进展过程中,外周器官和受体会受到损伤,神经细胞(如小胶质细胞)中的 P2X7R 表达会显著上调,从而增强感觉传入信息,使中枢神经系统敏感化,诱发或加剧疼痛。这些发现揭示了 ATP-P2X7R 信号轴在肿瘤和癌痛的发病机制中起着关键的调控作用,同时也具有治疗作用。因此,在本研究中,我们探讨了P2X7R在肿瘤和癌痛中的作用,讨论了抑制P2X7R活性(如使用拮抗剂)或阻断其表达在治疗肿瘤和癌痛中的药理特性,为今后治疗这两种疾病提供了重要依据。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
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