肿瘤细胞群体迁移中钙信号特征和机制探究.pdfVIP

肿瘤细胞群体迁移中钙信号特征和机制探究 钙离子作为细胞中的第二信使，有着多种多样的生物学功能；钙离子信号是由钙 离子通道、内钙库介导产生的细胞质钙离子浓度变化，是钙离子行使功能的主要途径 之一。肿瘤严重威胁到人类对美好生活的向往和对健康长寿的追求，肿瘤转移是肿瘤 晚期的主要标志，表现出由单一器官组织向全身蔓延发展的特征；肿瘤转移的方式有 很多，包括：单细胞运动、群体性细胞迁移，其中群体性细胞迁移的相关报道较少。 为了探究肿瘤细胞钙信号和群体迁移的关系，本文先对比了部分肿瘤上皮细胞的信号 模式，并着重分析了肺癌上皮细胞NCI-H292 的全细胞钙信号特征；然后通过药理学实 验探究了其钙信号来源，确定了胞外钙离子对钙信号形成的主导地位及内钙库的放大 调控作用；随后通过CCLE 数据库进一步缩小了目标通道的范围，并对可能的共性通 道TRPM7、STIM1/ORAI1 通道进行了siRNA 敲除，并做了信号分析，排除了这几种 通道在钙信号形成中的作用；最后在成球条件下，进一步探索了肿瘤细胞钙信号与群 体迁移之间的关系，说明了钙信号对细胞群体性迁移的调控作用。文章讨论了肿瘤上 皮细胞全细胞钙信号的特征，同时也讨论了钙离子信号、钙通道、群体迁移的关系， 为肿瘤治疗提供了新的思考。 关键词：活细胞成像、钙信号、钙离子通道、肿瘤、肿瘤群体迁移 Ⅰ Study on calcium signaling characteristics and mechanism in tumor collective cell migration As the second messenger in cells, calcium ion has a variety of biological functions. Calcium signal is a change in cytoplasmic calcium ion concentration mediated by calcium ion channels and internal calcium, which is one of the main ways for calcium ion to function. Cancer is a serious threat to human yearning for a better life and the pursuit of health and longevity. Cancer metastasis is the main sign of advanced cancer, showing the characteristic of spreading from a single organ to the whole body. There are many ways of cancer metastasis, including single cell movement and collective cell migration, among which the role of collective cell migration in cancer is rarely reported. In order to explore the relationship between tumor cell calcium signal and collective migration, this paper firstly compared the signal patterns of some tumor epithelial cells, and empHatically analyzed the whole-cell calcium signal characteristics of lung cancer epithelial cells NCI-H292. Then, the source of calcium signal was investigated throμgh pHarmacological experiments, and the dominant role of extracellμLar calcium ion on calcium signal formation and the amplification and regμLation of internal calcium rese