活体影像研究癌症进展和转移
Intravital imaging to study cancer progression and metastasis
原文发布日期:2022-11-16
DOI: 10.1038/s41568-022-00527-5
类型: Review Article
开放获取: 否
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Navigation through the bulk tumour, entry into the blood vasculature, survival in the circulation, exit at distant sites and resumption of proliferation are all steps necessary for tumour cells to successfully metastasize. The ability of tumour cells to complete these steps is highly dependent on the timing and sequence of the interactions that these cells have with the tumour microenvironment (TME), including stromal cells, the extracellular matrix and soluble factors. The TME thus plays a major role in determining the overall metastatic phenotype of tumours. The complexity and cause-and-effect dynamics of the TME cannot currently be recapitulated in vitro or inferred from studies of fixed tissue, and are best studied in vivo, in real time and at single-cell resolution. Intravital imaging (IVI) offers these capabilities, and recent years have been a time of immense growth and innovation in the field. Here we review some of the recent advances in IVI of mammalian models of cancer and describe how IVI is being used to understand cancer progression and metastasis, and to develop novel treatments and therapies. We describe new techniques that allow access to a range of tissue and cancer types, novel fluorescent reporters and biosensors that allow fate mapping and the probing of functional and phenotypic states, and the clinical applications that have arisen from applying these techniques, reporters and biosensors to study cancer. We finish by presenting some of the challenges that remain in the field, how to address them and future perspectives.
在肿瘤实体中穿行、进入血管系统、在循环系统中存活、远位定植并重启增殖——这些都是肿瘤细胞成功转移必需的步骤。肿瘤细胞完成这些步骤的能力高度依赖于它们与肿瘤微环境(包括基质细胞、细胞外基质和可溶性因子)发生相互作用的时机与顺序。因此,肿瘤微环境在决定肿瘤整体转移表型中起着重要作用。目前,肿瘤微环境的复杂性及因果动态关系无法在体外复现,也无法通过固定组织研究推断,最佳研究方式是在活体内以单细胞分辨率进行实时观察。活体成像技术具备这些能力,近年来该领域取得了巨大发展与创新。本文综述了哺乳动物癌症模型活体成像的最新进展,阐述了如何利用该技术理解癌症进展与转移机制,并开发新型治疗方法。我们介绍了可应用于多种组织和癌症类型的新型技术、能够实现细胞谱系追踪及功能和表型状态探测的新型荧光报告基因与生物传感器,以及这些技术、报告基因和生物传感器在癌症研究中的临床应用。最后,我们提出了该领域尚存的挑战、应对策略及未来展望。
Intravital imaging to study cancer progression and metastasis
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