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腺苷受体一瞥:抗肿瘤治疗的新靶点。

A glance at adenosine receptors: novel target for antitumor therapy.

作者信息

Merighi Stefania, Mirandola Prisco, Varani Katia, Gessi Stefania, Leung Edward, Baraldi Pier Giovanni, Tabrizi Mojgan Aghazadeh, Borea Pier Andrea

机构信息

Pharmacology Unit, Department of Clinical and Experimental Medicine, Via Fossato di Mortara 17-19, 44100, Ferrara, Italy.

出版信息

Pharmacol Ther. 2003 Oct;100(1):31-48. doi: 10.1016/s0163-7258(03)00084-6.

Abstract

Adenosine can be released from a variety of cells throughout the body, as the result of increased metabolic rates, in concentrations that can have a profound impact on the vasculature, immunoescaping, and growth of tumor masses. It is recognized that the concentrations of this nucleoside are increased in cancer tissues. Therefore, it is not surprising that adenosine has been shown to be a crucial factor in determining the cell progression pathway, either during apoptosis or during cytostatic state. From the perspective of cancer, the most important question then may be "Can activation and/or blockade of the pathways downstream of the adenosine receptor contribute to tumor development?" Rigorous examinations of the role of adenosine in in vivo and in vitro systems need to be investigated. The present review therefore proposes multiple adenosine-sustained ways that could prime tumor development together with the critical combinatorial role played by adenosine receptors in taking a choice between proliferation and death. This review proposes that adenosine acts as a potent regulator of normal and tumor cell growth. It is hypothesized that this effect is dependent on extracellular adenosine concentrations, cell surface expression of different adenosine receptor subtypes, and signal transduction mechanisms activated following the binding of specific agonists. We venture to suggest that the clarification of the role of adenosine and its receptors in cancer development may hold great promise for the treatment of chemotherapy in patients affected by malignancies.

摘要

由于代谢率增加,腺苷可从全身各种细胞中释放出来,其浓度可对脉管系统、免疫逃逸和肿瘤块的生长产生深远影响。人们认识到,这种核苷在癌组织中的浓度会升高。因此,腺苷已被证明是决定细胞在凋亡或细胞静止状态下的进展途径的关键因素,这并不奇怪。从癌症的角度来看,最重要的问题可能是“腺苷受体下游途径的激活和/或阻断是否会促进肿瘤发展?”需要对腺苷在体内和体外系统中的作用进行严格研究。因此,本综述提出了多种由腺苷维持的方式,这些方式可能引发肿瘤发展,以及腺苷受体在增殖和死亡之间做出选择时所起的关键组合作用。本综述提出,腺苷是正常细胞和肿瘤细胞生长的有效调节剂。据推测,这种作用取决于细胞外腺苷浓度、不同腺苷受体亚型的细胞表面表达以及特定激动剂结合后激活的信号转导机制。我们冒昧地提出,阐明腺苷及其受体在癌症发展中的作用可能为治疗受恶性肿瘤影响的患者的化疗带来巨大希望。

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