Roliano Gabriela Gonçalves, Azambuja Juliana Hofstätter, Brunetto Veronica Toniazzo, Butterfield Hannah Elizabeth, Kalil Antonio Nochi, Braganhol Elizandra
Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre 90050-170, Brazil.
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Cancers (Basel). 2022 Oct 6;14(19):4887. doi: 10.3390/cancers14194887.
Colorectal cancer (CRC) is among the most common cancers and exhibits a high fatality rate. Gut inflammation is related to CRC, with loss of homeostasis in immune cell activities. The cells of the innate and adaptive immune system, including macrophages, neutrophils, mast cells, and lymphocytes, are present in most solid tumors. Purinergic signaling allows for communication between immune cells within the tumor microenvironment (TME) and can alter the TME to promote tumor progression. This system is regulated by the availability of extracellular purines to activate purinoceptors (P1 and P2) and is tightly controlled by ectonucleotidases (E-NPP, CD73/CD39, ADA) and kinases, which interact with and modify nucleotides and nucleosides availability. In this review, we compiled articles detailing the relationship of the purinergic system with CRC progression. We found that increased expression of CD73 leads to the suppression of effector immune cell functions and tumor progression in CRC. The P1 family purinoceptors A1, A2A, and A2B were positively associated with tumor progression, but A2B resulted in increased cancer cell apoptosis. The P2 family purinoceptors P2X5, P2X7, P2Y, P2Y, and P2Y were factors primarily associated with promoting CRC progression. In summary, CD39/CD73 axis and the purinergic receptors exhibit diagnostic and prognostic value and have potential as therapeutic targets in CRC.
结直肠癌（CRC）是最常见的癌症之一，死亡率很高。肠道炎症与CRC相关，免疫细胞活动的体内平衡失调。先天性和适应性免疫系统的细胞，包括巨噬细胞、中性粒细胞、肥大细胞和淋巴细胞，存在于大多数实体瘤中。嘌呤能信号传导允许肿瘤微环境（TME）内的免疫细胞之间进行通讯，并可改变TME以促进肿瘤进展。该系统受细胞外嘌呤可用性的调节，以激活嘌呤受体（P1和P2），并由外核苷酸酶（E-NPP、CD73/CD39、ADA）和激酶严格控制，这些酶与核苷酸和核苷可用性相互作用并对其进行修饰。在这篇综述中，我们汇编了详细阐述嘌呤能系统与CRC进展关系的文章。我们发现，CD73表达增加会导致CRC中效应免疫细胞功能的抑制和肿瘤进展。P1家族嘌呤受体A1、A2A和A2B与肿瘤进展呈正相关，但A2B会导致癌细胞凋亡增加。P2家族嘌呤受体P2X5、P2X7、P2Y、P2Y和P2Y是主要与促进CRC进展相关的因素。总之，CD39/CD73轴和嘌呤能受体具有诊断和预后价值，并且在CRC中具有作为治疗靶点的潜力。
