文章：

免疫、炎症和癌症：腺苷的主要作用

Immunity, inflammation and cancer: a leading role for adenosine

原文发布日期：2013-11-14

DOI: 10.1038/nrc3613

类型: Review Article

开放获取: 否

要点：

1. Several lines of evidence highlight the importance of adenosine as a crucial regulatory autocrine and paracrine factor that accumulates in the neoplastic microenvironment.
2. The concentrations of adenosine, which is physiologically present at low levels in the interstitial fluids of unstressed tissues, can rapidly increase in response to pathological conditions, such as hypoxia, ischaemia, inflammation or trauma. After being released from the intracellular space into the extracellular space, adenosine functions as an 'alarm' or danger signal and, through the activation of specific receptors, it generates various cellular responses that aim to restore tissue homeostasis.
3. The persistence of increased adenosine levels beyond the acute injury phase can become detrimental to tissues because it can activate pathways that promote and maintain an unremitting wound-healing process. These pathways lead to fibrotic remodelling or trigger several immune and tissue reactions that promote neoplastic changes.
4. Extracellular adenosine, which is usually present at high concentrations in cancer tissues, is a crucial mediator in the alteration of immune cell functions in cancer. This is possibly because the tightly regulated adenosine receptor pathways of immune cells undergo substantial alterations in tumours, thereby switching the functions of these cells from immune surveillance and host defence to the promotion of cancer cell transformation and growth.
5. Beyond the task of providing an immune-tolerant tumour microenvironment by helping to determine the activity of immune and inflammatory cells, the adenosine system directly regulates cancer growth and metastatic dissemination through specific receptors that are expressed on cancer cells.
6. Although the strategy of counteracting the growth and progression of malignancies through the pharmacological modulation of adenosine receptors and/or metabolism has been shown to work in vitro and in animal models, the translation of these results into clinical practice will require a better understanding of how adenosine helps to determine the tumour milieu and the onset and progression of tumour growth in humans.

要点翻译：

1. 多项证据表明，腺苷作为一种关键的调节性自分泌和旁分泌因子，在肿瘤微环境中积累并发挥重要作用。
2. 在未受应激的组织间质液中，腺苷的生理浓度通常较低，但在缺氧、缺血、炎症或创伤等病理状态下会迅速升高。从细胞内空间释放到细胞外空间后，腺苷起着“警报”或危险信号的作用，并通过激活特定受体产生多种细胞反应，以恢复组织稳态。
3. 若腺苷水平在急性损伤期后持续升高，则可能对组织产生不利影响，因为它可能激活促进并维持持续性伤口愈合过程的通路。这些通路会导致纤维化重塑，或触发多种免疫和组织反应，进而促进肿瘤性改变。
4. 在癌组织中通常高浓度存在的细胞外腺苷，是改变癌症免疫细胞功能的关键介质。这可能是由于免疫细胞中严格调控的腺苷受体通路在肿瘤中发生显著改变，从而将这些细胞的功能从免疫监视和宿主防御转变为促进癌细胞转化和生长。
5. 腺苷系统除了通过决定免疫和炎症细胞的活性来提供免疫耐受的肿瘤微环境外，还通过癌细胞上表达的特定受体直接调节癌症生长和转移扩散。
6. 尽管通过药物调节腺苷受体和/或代谢来抑制恶性肿瘤生长和进展的策略已在体外和动物模型中证实有效，但要将这些结果转化为临床实践，还需要更深入地了解腺苷如何决定人类肿瘤微环境以及肿瘤生长的发生和发展。

英文摘要：

Cancer is a complex disease that is dictated by both cancer cell-intrinsic and cell-extrinsic processes. Adenosine is an ancient extracellular signalling molecule that can regulate almost all aspects of tissue function. As such, several studies have recently highlighted a crucial role for adenosine signalling in regulating the various aspects of cell-intrinsic and cell-extrinsic processes of cancer development. This Review critically discusses the role of adenosine and its receptors in regulating the complex interplay among immune, inflammatory, endothelial and cancer cells during the course of neoplastic disease.

摘要翻译： 

癌症是一种复杂疾病，由癌细胞内在和细胞外在过程共同支配。腺苷是一种古老的细胞外信号分子，几乎可以调控组织功能的所有方面。因此，近期多项研究强调了腺苷信号在调控癌症发展各方面细胞内在与外在过程中的关键作用。本文批判性地探讨了腺苷及其受体在肿瘤疾病进程中，如何调控免疫、炎症、内皮与癌细胞间复杂相互作用的角色。

原文链接：

Immunity, inflammation and cancer: a leading role for adenosine