Zefferino Roberto, Piccoli Claudia, Di Gioia Sante, Capitanio Nazzareno, Conese Massimo
Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy.
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.
Int J Mol Sci. 2021 Mar 4;22(5):2550. doi: 10.3390/ijms22052550.
Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: "Activating Invasion and Metastasis" and the "Avoiding Immune Destruction", with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.
连接蛋白和泛连接蛋白（Panx）形成的半通道（HCs）和间隙连接（GJs）与细胞外基质相互作用并进行间隙连接细胞间通讯（GJIC），因此它们参与癌症的发生以及向侵袭和转移的进展。当我们研究癌症时，忽略免疫系统以及忽视其在抵抗或 succumb to 早期肿瘤形成和进展直至微转移形成过程中的作用是不正确的，然而肿瘤微环境（TME）中真正发生的情况，即主要参与者以及哪些是肿瘤或机体的盟友，仍然不清楚。本文的目的是讨论关键参与者如何发挥作用，它们在“激活侵袭和转移”以及“避免免疫破坏”这两个重要过程中如何促进或抑制癌症进展，特别强调TME中GJIC、Panx - HCs和嘌呤能系统之间的相互作用，同时不忽视炎性小体及其衍生的细胞因子。特别是，针对致癌作用的早期/晚期阶段，讨论了Panx1/P2X7R信号体在肿瘤促进和/或抑制中的复杂且相互矛盾的作用。最后，考虑到癌细胞、基质细胞、免疫细胞在TME中的这种复杂相互作用，并关注它们的通讯方式，我们应该能够揭示有助于癌症生长的有害信息，并将它们转化为机体的盟友，从而设计出个性化的抗癌新治疗策略。
“succumb to”这里直接保留英文，因为中文语境下没有完全对应的简洁准确表述，需要结合上下文理解其意思大致为“在……方面失败”等类似含义。
