文章：

阐明转移过程

Illuminating the metastatic process

原文发布日期：2007-10-01

DOI: 10.1038/nrc2229

类型: Review Article

开放获取: 否

要点：

1. Metastasis is the spread of cancer from its site of origin and subsequent colonization of distant organs. Until recently, studying the details of this process has been difficult owing to the limited number of cells involved and the inaccessibility of the relevant anatomical sites.
2. Optical imaging enables the process of metastasis to be observed and studied directly. Resolution can vary from the level of whole tissues down to sub-cellular structures depending on the imaging method.
3. In addition to detecting tumour cells, imaging can provide information about cell movement, interactions between cells, the activity of proteins or signalling pathways, and blood and lymphatic flow.
4. Very few cells within primary tumours are motile, and these move rapidly with an amoeboid morphology.
5. Metastatic cells are better at entering the blood vessels and withstanding shear stress than their non-metastatic counterparts.
6. Cells lodge in capillaries by various mechanisms, including physical constraint, aggregation with platelets and active interactions with the endothelium.
7. Apoptosis of tumour cells shortly after arriving at secondary sites is a major source of inefficiency in the metastatic process.
8. Certain tumour types preferentially metastasize to particular secondary sites, and the distribution of metastases cannot solely be accounted for by the pattern of blood flow. The molecular basis of this phenomenon is not well understood.
9. Imaging can be used in the preclinical evaluation of drugs that target steps in the metastatic process.

要点翻译：

1. 转移是指癌细胞从原发部位扩散并在远端器官定植的过程。由于参与该过程的细胞数量有限且相关解剖部位难以观察，直至近期研究者仍难以深入探究其细节。
2. 光学成像技术使得直接观察和研究转移过程成为可能。根据成像方法的不同，分辨率可从整体组织层面至亚细胞结构级别。
3. 除检测肿瘤细胞外，成像技术还能提供细胞运动、细胞间相互作用、蛋白质或信号通路活性以及血液和淋巴流动等信息。
4. 原发肿瘤中具有运动能力的细胞极少，这些细胞以阿米巴样形态快速移动。
5. 与非转移性细胞相比，转移性细胞更擅长进入血管并耐受剪切应力。
6. 细胞通过多种机制滞留于毛细血管，包括物理约束、与血小板聚集以及与内皮细胞的主动相互作用。
7. 肿瘤细胞抵达继发部位后不久发生的细胞凋亡是导致转移过程效率低下的主要因素。
8. 特定肿瘤类型会优先转移至某些继发部位，仅凭血流分布模式无法完全解释这种转移分布规律，其分子机制尚未得到充分阐释。
9. 成像技术可用于靶向转移过程关键环节药物的临床前评估。

英文摘要：

Until recently most studies of metastasis only measured the end point of the process — macroscopic metastases. Although these studies have provided much useful information, the details of the metastatic process remain somewhat mysterious owing to difficulties in studying cell behaviour with high spatial and temporal resolution in vivo. The use of luminescent and fluorescent proteins and developments in optical imaging technology have enabled the direct observation of cancer cells spreading from their site of origin and arriving at secondary sites. This Review will describe recent advances in our understanding of the different steps of metastasis gained from cellular resolution imaging, and how these techniques can be used in preclinical drug evaluation.

摘要翻译： 

直到最近，大多数关于转移的研究仅测量了该过程的终点——肉眼可见的转移灶。尽管这些研究提供了许多有用的信息，但由于难以在活体中以高空间和时间分辨率研究细胞行为，转移过程的细节仍然有些神秘。发光和荧光蛋白的使用以及光学成像技术的发展使得直接观察癌细胞从其起源部位扩散并到达继发部位成为可能。本综述将描述我们通过细胞分辨率成像获得的关于转移不同步骤理解的最新进展，以及这些技术如何用于临床前药物评估。

原文链接：

Illuminating the metastatic process