Deli Tamás, Csernoch László
Department of Physiology, Research Centre for Molecular Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary.
Pathol Oncol Res. 2008 Sep;14(3):219-31. doi: 10.1007/s12253-008-9071-7. Epub 2008 Jun 25.
Purinergic signal transduction mechanisms have been appreciated as a complex intercellular signalling network that plays an important regulatory role in both short- and long-term processes in practically every living cell. One of the most intriguing aspects of the field is the participation of ATP and other purine nucleotides in the determination of cell fate and the way they direct cells towards proliferation, differentiation or apoptosis, thereby possibly taking part in promoting or preventing malignant transformation. In this review, following a very brief introduction to the historical aspects of purinergic signalling and a concise overview of the structure of and signal transduction pathways coupled to P2 purinergic receptors, the current theories concerning the possible ways how extracellular ATP can alter the function of tumour cells and the effectiveness of anticancer therapies are discussed, including pharmacological, nutritional, vasoactive and 'anti-antioxidant' actions of the nucleotide. The effects of ATP on animals inoculated with human tumours and on patients with cancer are looked over next, and then an overview of the literature regarding the expression and presumed functions of P2 purinoceptors on tumour cells in vitro is presented, sorted out according to the relevant special clinical fields. The article is closed by reviewing the latest developments in the diagnostic use of P2 purinergic receptors as tumour markers and prognostic factors, while discussing some of the difficulties and pitfalls of the therapeutic use of ATP analogues.
嘌呤能信号转导机制被认为是一个复杂的细胞间信号网络，在几乎每个活细胞的短期和长期过程中都发挥着重要的调节作用。该领域最引人入胜的方面之一是ATP和其他嘌呤核苷酸参与细胞命运的决定，以及它们引导细胞增殖、分化或凋亡的方式，从而可能参与促进或预防恶性转化。在这篇综述中，在对嘌呤能信号的历史方面进行非常简要的介绍以及对与P2嘌呤能受体偶联的结构和信号转导途径进行简要概述之后，讨论了关于细胞外ATP如何改变肿瘤细胞功能以及抗癌治疗有效性的当前理论，包括核苷酸的药理学、营养、血管活性和“抗抗氧化剂”作用。接下来审视了ATP对接种人类肿瘤的动物和癌症患者的影响，然后根据相关特殊临床领域，对关于P2嘌呤受体在体外肿瘤细胞上的表达和假定功能的文献进行了综述。文章最后回顾了P2嘌呤能受体作为肿瘤标志物和预后因素在诊断应用方面的最新进展，同时讨论了ATP类似物治疗应用中的一些困难和陷阱。
