McMillen Patrick, Oudin Madeleine J, Levin Michael, Payne Samantha L
Department of Biology, Allen Discovery Center, Tufts University, Medford, MA, United States.
Department of Biomedical Engineering, Tufts University, Medford, MA, United States.
Front Cell Dev Biol. 2021 Sep 21;9:739024. doi: 10.3389/fcell.2021.739024. eCollection 2021.
Cellular communication is important in all aspects of tissue and organism functioning, from the level of single cells, two discreet populations, and distant tissues of the body. Long distance communication networks integrate individual cells into tissues to maintain a complex organism during development, but when communication between cells goes awry, disease states such as cancer emerge. Herein we discuss the growing body of evidence suggesting that communication methods known to be employed by neurons, also exist in other cell types. We identify three major areas of long-distance communication: bioelectric signaling, tunneling nanotubes (TNTs), and macrophage modulation of networks, and draw comparisons about how these systems operate in the context of development and cancer. Bioelectric signaling occurs between cells through exchange of ions and tissue-level electric fields, leading to changes in biochemical gradients and molecular signaling pathways to control normal development and tumor growth and invasion in cancer. TNTs transport key morphogens and other cargo long distances, mediating electrical coupling, tissue patterning, and malignancy of cancer cells. Lastly macrophages maintain long distance signaling networks through trafficking of vesicles during development, providing communication relays and priming favorable microenvironments for cancer metastasis. By drawing comparisons between non-neural long distance signaling in the context of development and cancer we aim to encourage crosstalk between the two fields to cultivate new hypotheses and potential therapeutic strategies.
细胞通讯在组织和机体功能的各个方面都很重要,从单细胞水平、两个离散的细胞群体到身体的远距离组织。长距离通讯网络将单个细胞整合到组织中,以在发育过程中维持复杂的机体,但当细胞间通讯出现问题时,诸如癌症等疾病状态就会出现。在此,我们讨论越来越多的证据表明,已知神经元所采用的通讯方式也存在于其他细胞类型中。我们确定了长距离通讯的三个主要领域:生物电信号传导、隧道纳米管(TNTs)以及巨噬细胞对网络的调节,并比较了这些系统在发育和癌症背景下的运作方式。生物电信号传导通过离子交换和组织水平的电场在细胞间发生,导致生化梯度和分子信号通路的变化,以控制正常发育以及癌症中的肿瘤生长和侵袭。TNTs可长距离运输关键形态发生素和其他物质,介导电耦合、组织模式形成以及癌细胞的恶性转化。最后,巨噬细胞在发育过程中通过囊泡运输维持长距离信号网络,为癌症转移提供通讯中继并引发有利的微环境。通过比较发育和癌症背景下的非神经长距离信号传导,我们旨在促进这两个领域之间的相互交流,以培养新的假说和潜在的治疗策略。