Under nonpathological conditions, the extracellular nucleotide concentration remains constant and low (nM range) because of a close balance between ATP release and ATP consumption. This balance is completely altered in cancer disease. Adenine and uridine nucleotides are found in the extracellular space of tumors in high millimolar (mM) concentrations acting as extracellular signaling molecules. In general, although uridine nucleotides may be involved in different tumor cell responses, purinergic signaling in cancer is preferentially focused on adenine nucleotides and nucleosides. Extracellular ATP can bind to specific receptors (P receptors) triggering different responses, or it can be hydrolyzed by ectoenzymes bound to cell membranes to render the final product adenosine. The latter pathway plays an important role in the increase of adenosine in tumor microenvironment. In this study, we will focus on extracellular ATP and adenosine, their effects acting as ligands of specific receptors, activating ectoenzymes, and promoting epithelial–mesenchymal transition, migration, and invasion in cancer cells. Finding the roles that these nucleotides play in tumor microenvironment may be important to design new intervention strategies in cancer therapies.

中文翻译：

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肿瘤微环境中的细胞外 ATP 和腺苷：在上皮-间质转化、细胞迁移和侵袭中的作用

在非病理条件下，由于 ATP 释放和 ATP 消耗之间的密切平衡，细胞外核苷酸浓度保持恒定且较低（nM 范围）。这种平衡在癌症疾病中完全改变。腺嘌呤和尿苷核苷酸以高毫摩尔 (mM) 浓度存在于肿瘤的细胞外空间，充当细胞外信号分子。一般来说，虽然尿苷核苷酸可能参与不同的肿瘤细胞反应，但癌症中的嘌呤能信号传导优先集中在腺嘌呤核苷酸和核苷上。细胞外 ATP 可以与特定受体（P 受体）结合，触发不同的反应，或者它可以被与细胞膜结合的胞外酶水解，从而产生最终产物腺苷。后一种途径在肿瘤微环境中腺苷的增加中起重要作用。在这项研究中，我们将重点关注细胞外 ATP 和腺苷，它们作为特定受体配体的作用，激活胞外酶，促进癌细胞的上皮-间质转化、迁移和侵袭。发现这些核苷酸在肿瘤微环境中的作用对于设计癌症治疗的新干预策略可能很重要。