Redox Biology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack - 753003, India.
Curr Cancer Drug Targets. 2018;18(6):514-521. doi: 10.2174/1568009618666171129222637.
Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is a class of diseases characterized by uncontrolled cell growth that eventually invade other tissues and develop secondary malignant growth at other sites by metastasis. Intercellular communication plays a major role in cancer, particularly in the process of cell proliferation and coordination which in turn leads to tumor invasion, metastasis and development of resistance to therapy. Cells communicate among themselves in a variety of ways, namely: i) via gap junctions with adjacent cells; ii) via exosomes with nearby cells; and iii) via chemical messengers with distant cells. Besides, cell - cell connection by tunneling nanotubes (TnTs) is recently gaining importance where intercellular components are transferred between cells. In general cell organelles like Golgi vesicle and mitochondria; and biomolecules like nucleic acids and proteins are transferred through these TnTs. These TnTs are long cytoplasmic extensions made up of actin that function as intercellular bridge and connect a wide variety of cell types. Malignant cells form TnTs with either other malignant cells or cells of the surrounding tumor matrix. These TnTs help in the process of initiation of tumor formation, its organization and propagation. The current review focuses on the role of TnTs mediated cell - cell signaling in cancer micro-environment. Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis.
目前癌症是全球主要的死亡原因。恶性肿瘤或癌症是一类以失控细胞生长为特征的疾病,最终会通过转移侵犯其他组织,并在其他部位形成继发性恶性生长。细胞间通讯在癌症中起着重要作用,特别是在细胞增殖和协调的过程中,这反过来又导致肿瘤侵袭、转移和对治疗的耐药性发展。细胞通过多种方式相互通讯,即:i)通过与相邻细胞的间隙连接;ii)通过与附近细胞的外泌体;iii)通过与远处细胞的化学信使。此外,细胞 - 细胞连接通过隧道纳米管(TnTs)最近变得越来越重要,其中细胞间成分在细胞之间转移。通常,细胞细胞器如高尔基体囊泡和线粒体;以及生物分子如核酸和蛋白质通过这些 TnTs 转移。这些 TnTs 是由肌动蛋白组成的长细胞质延伸,作为细胞间桥发挥作用,并连接各种细胞类型。恶性细胞与其他恶性细胞或周围肿瘤基质的细胞形成 TnTs。这些 TnTs 有助于肿瘤形成、组织和传播的过程。本综述重点介绍了 TnTs 介导的细胞间信号在癌症微环境中的作用。抑制 TnT 形成的药物,如二甲双胍和依维莫司,可以针对 TnTs 用于癌症生长、增殖、肿瘤侵袭和转移的治疗。