文章：

活老鼠癌症的影像特征

Imaging hallmarks of cancer in living mice

原文发布日期：2014-05-23

DOI: 10.1038/nrc3742

类型: Review Article

开放获取: 否

要点：

1. Our current view on cancer hallmarks is mostly based on techniques that provide a snapshot of a large population of cells, whereas intravital microscopy (IVM) provides a view on dynamic subpopulations of both tumour and stromal cells in living animals.
2. Imaging windows allow longitudinal studies on optically inaccessible tumour tissue during consecutive imaging sessions. Most imaging windows are used to study primary tumours, but some allow for the examination of metastases.
3. To acquire high-quality fluorescent images deep inside animals, multiphoton microscopes are frequently used. The advantages of multiphoton microscopes include deep tissue penetration, reduced phototoxicity and reduced bleaching, optical sectioning and reduced tissue-mediated absorption and scattering.
4. Several contrast agents and fluorescent biosensors are available to intravitally image the activation status of multiple proteins and signalling pathways in individual cells, deep inside animals.
5. IVM demonstrated a paradoxical role of the tumour vasculature by showing that, in some cases, leaky vessels can prevent the delivery of therapeutic agents owing to elevated interstitial fluid pressure but, in other cases, leaky vessels can support the delivery of drugs.
6. Intravital imaging is a powerful tool to investigate the paradoxical role of the immune system on tumour growth and could help to clarify the best approach to stimulate the immune destruction of tumours and prevent pro-tumorigenic immune effects.
7. Intravital lineage tracing can uncover the dynamic nature of cancer stem cells and provides information on the history and fate of these cells.
8. IVM has the potential to identify the targets of cancer therapeutics and validate the in vivo mode of actions of these drugs, for example, those that inhibit proliferation or promote cell death.
9. Combining fluorescence IVM techniques with various imaging and conventional biochemical techniques holds great promise to gain further insight into the molecular mechanisms that underlie the hallmarks of cancer.

要点翻译：

1. 我们目前对癌症特征的认识主要基于对大量细胞群体进行快照分析的技术，而活体显微镜技术则能在活体动物中动态观察肿瘤细胞和基质细胞的亚群。
2. 成像窗口技术使得在连续成像过程中对光学不可及的肿瘤组织进行纵向研究成为可能。大多数成像窗口用于研究原发性肿瘤，但部分也可用于观察转移灶。
3. 为获取动物体内深部的高质量荧光图像，多光子显微镜被广泛使用。其优势包括深层组织穿透能力、较低的光毒性和光漂白效应、光学切片功能以及减少组织介导的吸收和散射现象。
4. 多种对比剂和荧光生物传感器的应用，使得在活体动物深层组织中单细胞水平实时观测多种蛋白质及信号通路的激活状态成为可能。
5. 活体显微镜研究揭示了肿瘤血管系统的矛盾作用：在某些情况下，渗漏血管会因间质流体压力升高而阻碍治疗药物递送；但在另一些情况下，血管渗漏反而有助于药物输送。
6. 活体成像技术是探索免疫系统对肿瘤生长矛盾影响的有力工具，有助于阐明最佳策略来激活免疫系统摧毁肿瘤，同时阻止促肿瘤生成的免疫效应。
7. 活体谱系追踪技术能够揭示癌症干细胞群体的动态特性，并提供这些细胞的历史渊源与命运归宿信息。
8. 活体显微镜技术具有识别癌症治疗靶点的潜力，并能验证药物在体内的作用机制，例如那些抑制增殖或促进细胞死亡的药物。
9. 将荧光活体显微镜技术与多种成像及传统生化技术相结合，有望更深入地揭示癌症特征背后的分子机制。

英文摘要：

To comprehend the complexity of cancer, the biological characteristics acquired during the initiation and progression of tumours were classified as the 'hallmarks of cancer'. Intravital microscopy techniques have been developed to study individual cells that acquire these crucial traits, by visualizing tissues with cellular or subcellular resolution in living animals. In this Review, we highlight the latest intravital microscopy techniques that have been used in living animals (predominantly mice) to unravel fundamental and dynamic aspects of various hallmarks of cancer. In addition, we discuss the application of intravital microscopy techniques to cancer therapy, as well as limitations and future perspectives for these techniques.

摘要翻译： 

为了理解癌症的复杂性，肿瘤在发生和进展过程中所获得的生物学特征被归类为“癌症的标志”。活体显微技术已被开发用于研究获得这些关键特征的单个细胞，通过在活体动物中以细胞或亚细胞分辨率观察组织。在本综述中，我们重点介绍了最新的活体显微技术，这些技术已被用于活体动物（主要是小鼠）中，以揭示癌症各种标志的基本和动态方面。此外，我们还讨论了活体显微技术在癌症治疗中的应用，以及这些技术的局限性和未来前景。

原文链接：

Imaging hallmarks of cancer in living mice