Lou Emil, Zhai Edward, Sarkari Akshat, Desir Snider, Wong Phillip, Iizuka Yoshie, Yang Jianbo, Subramanian Subbaya, McCarthy James, Bazzaro Martina, Steer Clifford J
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, United States.
Front Cell Dev Biol. 2018 Oct 2;6:95. doi: 10.3389/fcell.2018.00095. eCollection 2018.
Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components. The transport of cargo via TNTs occurs between malignant and stromal cells and can lead to changes in gene regulation that propagate the cancer phenotype. More notably, the transfer of these varied molecules almost invariably plays a critical role in the communication between cancer cells themselves in an effort to resist death by chemotherapy and promote the growth and metastases of the primary oncogenic cell. The more traditional definition of "Systems Biology" is the computational and mathematical modeling of complex biological systems. The concept, however, is now used more widely in biology for a variety of contexts, including interdisciplinary fields of study that focus on complex interactions within biological systems and how these interactions give rise to the function and behavior of such systems. In fact, it is imperative to understand and reconstruct components in their native context rather than examining them separately. The long-term objective of evaluating cancer ecosystems in their proper context is to better diagnose, classify, and more accurately predict the outcome of cancer treatment. Communication is essential for the advancement and evolution of the tumor ecosystem. This interplay results in cancer progression. As key mediators of intercellular communication within the tumor ecosystem, TNTs are the central topic of this article.
细胞间通讯对于癌细胞组织和侵袭的生态系统至关重要。识别关键的细胞货物及其多样的运输方式是理解癌细胞生长基本机制的重要考量因素。间隙连接、外泌体和凋亡小体作为介导细胞间运输的物理方式发挥着关键作用。隧道纳米管（TNTs）——基于肌动蛋白的狭窄细胞质延伸结构——是独特的结构，可促进包括微小RNA、线粒体和多种其他亚细胞成分在内的货物进行直接、长距离的细胞间运输。通过TNTs进行的货物运输发生在恶性细胞和基质细胞之间，并可导致基因调控的变化，从而传播癌症表型。更值得注意的是，这些多样分子的转移几乎总是在癌细胞自身之间的通讯中发挥关键作用，以努力抵抗化疗导致的死亡并促进原发性致癌细胞的生长和转移。“系统生物学”更传统的定义是对复杂生物系统进行计算和数学建模。然而，现在这个概念在生物学中被更广泛地用于各种背景，包括专注于生物系统内复杂相互作用以及这些相互作用如何产生此类系统的功能和行为的跨学科研究领域。事实上，必须在其天然背景下理解和重建组件，而不是单独对其进行研究。在适当背景下评估癌症生态系统的长期目标是更好地诊断、分类并更准确地预测癌症治疗的结果。通讯对于肿瘤生态系统的发展和演变至关重要。这种相互作用导致癌症进展。作为肿瘤生态系统内细胞间通讯的关键介质，TNTs是本文讨论的核心主题。
