Extracellular vesicles (EVs), mainly classified as small and large EVs according to their size/origin, contribute as multi-signal messengers to intercellular communications in normal/pathological conditions. EVs are now recognized as critical players in cancer processes by promoting transformation, growth, invasion, and drug-resistance of tumor cells thanks to the release of molecules contained inside them (i.e., nucleic acids, lipids and proteins) into the tumor microenvironment (TME). Interestingly, secretion from donor cells and/or uptake of EVs/their content by recipient cells are regulated by extracellular signals present in TME. Among those able to modulate the EV-tumor crosstalk, purines, mainly the adenine-based ones, could be included. Indeed, TME is characterized by high levels of ATP/adenosine and by the presence of enzymes deputed to their turnover. Moreover, ATP/adenosine, interacting with their own receptors, can affect both host and tumor responses. However, studies on whether/how the purinergic system behaves as a modulator of EV biogenesis, release and functions in cancer are still poor. Thus, this review is aimed at collecting data so far obtained to stimulate further research in this regard. Hopefully, new findings on the impact of adenine purines/related enzymes on EV functions may be exploited in tumor management uncovering novel tumor biomarkers and/or druggable targets.

中文翻译：

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基于腺嘌呤的嘌呤和相关的代谢酶：它们对肿瘤细胞外囊泡活动的影响的证据。

细胞外囊泡（EV），根据其大小/来源，主要分为小型和大型EV，它们在正常/病理条件下作为多信号信使参与细胞间通讯。电动汽车由于其内部所包含的分子（即核酸，脂质和蛋白质）释放到肿瘤微环境（TME）中，因此通过促进肿瘤细胞的转化，生长，侵袭和耐药性，现已被认为是癌症过程中的关键角色）。有趣的是，供体细胞的分泌和/或受体细胞对EV的吸收/它们的含量受TME中存在的细胞外信号调节。在能够调节EV-肿瘤串扰的那些药物中，可以包括嘌呤，主要是基于腺嘌呤的嘌呤。确实，TME的特征是高水平的ATP /腺苷和存在代表其周转率的酶。而且，ATP /腺苷与它们自己的受体相互作用，可以影响宿主和肿瘤反应。然而，关于嘌呤能系统是否/如何充当EV生物发生，释放和癌症功能的调节剂的研究仍然很薄。因此，本综述旨在收集迄今为止获得的数据，以刺激这方面的进一步研究。希望，可以在肿瘤治疗中利用有关腺嘌呤嘌呤/相关酶对EV功能的影响的新发现，从而发现新颖的肿瘤生物标志物和/或可药物化靶标。嘌呤能系统是否/如何作为EV生物发生，释放和癌症功能的调节剂的研究仍然很薄。因此，本综述旨在收集迄今为止获得的数据，以刺激这方面的进一步研究。希望，可以在肿瘤治疗中利用有关腺嘌呤嘌呤/相关酶对EV功能的影响的新发现，从而发现新颖的肿瘤生物标志物和/或可药物化靶标。嘌呤能系统是否/如何作为EV生物发生，释放和癌症功能的调节剂的研究仍然很薄。因此，本综述旨在收集迄今为止获得的数据，以刺激这方面的进一步研究。希望，可以在肿瘤治疗中利用有关腺嘌呤嘌呤/相关酶对EV功能的影响的新发现，从而发现新颖的肿瘤生物标志物和/或可药物化靶标。