Medical School, Federal University of Fronteira Sul, Rodovia SC 484 - Km 02, Fronteira Sul, Chapecó, SC, CEP 89815-899, Brazil.
Postgraduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Rodovia SC 484 - Km 02, Fronteira Sul, Chapecó, SC, CEP 89815-899, Brazil.
Purinergic Signal. 2021 Jun;17(2):179-200. doi: 10.1007/s11302-020-09760-9. Epub 2021 Feb 12.
Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.
乳腺癌（BC）是女性死亡的最常见原因，是一个全球性的公共卫生问题。在这里，我们旨在讨论嘌呤能系统与 BC 之间的相关性，以确定治疗靶点。为此，我们分析了细胞外核苷酸和核苷与嘌呤能受体 P1 和 P2 的相互作用，以及胞外核苷酸酶（CD39 和 CD73）对肿瘤进展的影响。进行了全面的文献检索。在 PubMed、Scielo、Lilacs 和 ScienceDirect 数据库中找到了与本综述相关的文章。结果表明，在 P1 受体中，A1、A2A 和 A2B 受体参与了 BC 的增殖和侵袭，而 A3 受体与肿瘤生长的抑制有关。在 P2 受体中，P2X7 具有双重功能。短时间激活时促进转移，但长时间激活时与 BC 细胞死亡有关。P2Y2 和 P2Y6 受体与 BC 的增殖和侵袭有关。此外，BC 中 CD39 和 CD73 的高表达与预后较差密切相关。涉及的受体和胞外核苷酸酶可能成为治疗靶点。已经发现几种嘌呤能途径参与了 BC 细胞的存活和进展。在本综述中，除了分析涉及的途径外，我们还回顾了与嘌呤能系统相关的已经研究过的用于 BC 的治疗干预措施，以及其他可能的治疗靶点。
