Extracellular purines, purinergic receptors and tumor growth.
Extracellular purines, purinergic receptors and tumor growth.
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细胞外嘌呤，嘌呤能受体和肿瘤生长。
DOI：
10.1038/onc.2016.206
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发表时间：
2017-01-19
期刊：
影响因子：
8
通讯作者：
Adinolfi E
中科院分区：
文献类型：
--
作者：
Di Virgilio F;Adinolfi E
实际上，所有肿瘤细胞以及所有免疫细胞表达细胞外核苷（腺苷）和核苷酸（ATP、ADP、UTP、UDP和糖UDP）的质膜受体。肿瘤微环境的特征在于异常高浓度的ATP和腺苷。腺苷是免疫抑制肿瘤环境的主要决定因素。由CD 39和CD 73催化的细胞外ATP的顺序水解是肿瘤细胞中腺苷产生的主要途径。细胞外ATP和腺苷塑造宿主和肿瘤的反应。根据激活的特异性受体，细胞外嘌呤介导宿主侧的免疫抑制或免疫刺激，以及肿瘤侧的生长刺激或细胞毒性。这一领域的最新进展为解码这一复杂场景提供了关键，并为利用治疗的潜在益处奠定了基础。临床前数据显示，靶向腺苷生成途径（即CD 73）或腺苷能受体（即A2 A）可缓解免疫抑制并有效抑制肿瘤生长。另一方面，通过靶向癌症和免疫细胞的P2 X7 ATP选择性受体，实验性肿瘤的生长被强烈抑制。本文综述了细胞外嘌呤（嘌呤能信号）在宿主-肿瘤相互作用中所起作用的最新数据，并强调了该领域最新进展所产生的新治疗选择。
Virtually, all tumor cells as well as all immune cells express plasma membrane receptors for extracellular nucleosides (adenosine) and nucleotides (ATP, ADP, UTP, UDP and sugar UDP). The tumor microenvironment is characterized by an unusually high concentration of ATP and adenosine. Adenosine is a major determinant of the immunosuppressive tumor milieu. Sequential hydrolysis of extracellular ATP catalyzed by CD39 and CD73 is the main pathway for the generation of adenosine in the tumor interstitium. Extracellular ATP and adenosine mold both host and tumor responses. Depending on the specific receptor activated, extracellular purines mediate immunosuppression or immunostimulation on the host side, and growth stimulation or cytotoxicity on the tumor side. Recent progress in this field is providing the key to decode this complex scenario and to lay the basis to harness the potential benefits for therapy. Preclinical data show that targeting the adenosine-generating pathway (that is, CD73) or adenosinergic receptors (that is, A2A) relieves immunosuppresion and potently inhibits tumor growth. On the other hand, growth of experimental tumors is strongly inhibited by targeting the P2X7 ATP-selective receptor of cancer and immune cells. This review summarizes the recent data on the role played by extracellular purines (purinergic signaling) in host–tumor interaction and highlights novel therapeutic options stemming from recent advances in this field.