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anoikis

肿瘤

关键词肿瘤 临床研究术语 细胞凋亡

词汇介绍

拓展阅读

解析

Anoikis 

       n. 失巢凋亡现象;失巢凋亡;

       Similarly, in a mouse model of ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth. 同样,在卵巢癌小鼠模型中,抑制应激和相关的去甲肾上腺素和肾上腺素增加可防止肿瘤细胞发生失巢凋亡,从而促进肿瘤生长。

概述

正常上皮细胞或不具备转移性质的实体瘤细胞从原位脱落进入血流后就会引发细胞凋亡,这种在脱离原来生存环境的特殊情况下发生的细胞凋亡成为失巢凋亡。这种现象在某些细胞分化生长周期短、组织更新快的细胞中表现更为明显。如小肠上皮是人体内更新最快的组织之一,小肠上皮细胞从基膜移动到上皮只需要6-7天的时间,小肠上皮细胞的生长和分化对基膜的依赖型更为明显。因此,一旦发生脱落,细胞就很容易发生凋亡。除上皮细胞和内皮细胞外,其他类型的细胞也会出现失巢凋亡现象,如骨骼肌细胞、某些致瘤潜力低的黑色素瘤细胞以及胚胎成

Acquisition of cancer stem cell-like properties in human small airway epithelial cells after a longterm exposure to carbon nanomaterials复制标题

长期暴露于碳纳米材料后获得人类小气道上皮细胞的肿瘤干细胞样特性

发表时间:2019-07-01

影响因子:7.7

作者: Chayanin Kiratipaiboon

期刊:Environ Sci Nano

Cancer stem cells (CSCs) are a key driver of tumor formation and metastasis, but how they are affected by nanomaterials is largely unknown. The present study investigated the effects of different carbon-based nanomaterials (CNMs) on neoplastic and CSC-like transformation of human small airway epithelial cells and determined the underlying mechanisms. Using a physiologically relevant exposure model (long-term/low-dose) with system validation using a human carcinogen, asbestos, we demonstrated that single-walled carbon nanotubes, multi-walled carbon nanotubes, ultrafine carbon black, and crocidolite asbestos induced particle-specific anchorage-independent colony formation, DNA-strand break, and p53 downregulation, indicating genotoxicity and carcinogenic potential of CNMs. The chronic CNM-exposed cells exhibited CSC-like properties as indicated by 3D spheroid formation, anoikis resistance, and CSC markers expression. Mechanistic studies revealed specific self-renewal and epithelial-mesenchymal transition (EMT)-related transcription factors that are involved in the cellular transformation process. Pathway analysis of gene signaling networks supports the role of SOX2 and SNAI1 signaling in CNM-mediated transformation. These findings support the potential carcinogenicity of high aspect ratio CNMs and identified molecular targets and signaling pathways that may contribute to the disease development.

译文

癌症干细胞(CSCs)是肿瘤形成和转移的关键驱动因素,但它们如何受到纳米材料的影响尚不清楚。本研究调查了不同碳基纳米材料(CNMs)对人小气道上皮细胞的肿瘤和CSC样转化的影响,并确定了其潜在的机制。使用生理相关的暴露模型(长期/低剂量)和使用人类致癌物质石棉的系统验证,我们证明了单壁碳纳米管,多壁碳纳米管,超细炭黑和青石棉石棉诱导颗粒 - 特定的不依赖于锚定的集落形成,DNA链断裂和p53下调,表明CNM的遗传毒性和致癌潜力。慢性CNM暴露的细胞表现出类似CSC的性质,如3D球状体形成,失巢凋亡抗性和CSC标志物表达所示。机理研究揭示了参与细胞转化过程的特异性自我更新和上皮 - 间质转化(EMT)相关的转录因子。基因信号传导网络的途径分析支持SOX2和SNAI1信号传导在CNM介导的转化中的作用。这些发现支持高纵横比CNM的潜在致癌性,并确定可能有助于疾病发展的分子靶标和信号传导途径。