文章：

肿瘤细胞运动的活体成像

Intravital imaging of cell movement in tumours

原文发布日期：2003-12-01

DOI: 10.1038/nrc1231

类型: Review Article

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要点：

1. Carcinoma cells in the primary tumour can move at up to 10 times the velocity of similar cells in vitro.
2. The highest velocities are observed for carcinoma cells in metastatic tumours that are moving along linear paths in association with extracellular-matrix (ECM) fibres.
3. Carcinoma cell motility is characterized as solitary amoeboid movement and is unrestricted by networks of ECM in mammary tumours.
4. Carcinoma cell motility is restricted at the basement membrane of blood vessels, where the cells must squeeze through small pores in the basement membrane/endothelium to gain access to the blood space.
5. Carcinoma cells in non-metastatic tumours are fragmented during intravasation as they squeeze across the basement membrane/endothelium, whereas carcinoma cells in metastatic tumours cross this restriction as intact cells.
6. Carcinoma cells in metastatic tumours are attracted to blood vessels, where they form a layer of cells that are morphologically polarized towards the vessel.
7. Chemotaxis to epidermal growth factor is shown by carcinoma cells in vitro and in vivo in primary tumours, and might be responsible for the attraction of carcinoma cells to blood vessels.
8. Cell polarity towards blood vessels is correlated with increased intravasation and metastasis.
9. The ECM and its interaction with carcinoma cells can be observed directly using the second harmonic signal from multiphoton-illuminated tumours.
10. Metastatic mammary tumours contain large numbers of rapidly moving macrophages and other leukocytes near blood vessels. These might be a source of chemotactic cytokines.
11. Intravital imaging can be productively correlated with gene-expression profiling to generate new insights into the pathways that are responsible for invasive-cell behaviour.

要点翻译：

1. 原发性肿瘤中的癌细胞的移动速度可达体外类似细胞的10倍。
2. 在转移性肿瘤中，癌细胞沿细胞外基质（ECM）纤维呈线性路径移动时观察到最高速度。
3. 癌细胞的运动特征为独立的阿米巴样运动，在乳腺肿瘤中不受ECM网络的限制。
4. 癌细胞的运动在血管基底膜处受限，细胞必须挤压穿过基底膜/内皮的小孔才能进入血液空间。
5. 非转移性肿瘤中的癌细胞在穿越基底膜/内皮时会发生碎裂，而转移性肿瘤中的癌细胞则以完整细胞形式穿越此限制。
6. 转移性肿瘤中的癌细胞被血管吸引，形成一层形态上向血管极化的细胞层。
7. 体外和体内原发性肿瘤中的癌细胞显示出对表皮生长因子的趋化性，这可能是癌细胞被血管吸引的原因。
8. 向血管的细胞极性与增加的血管内渗和转移相关。
9. 利用多光子激发肿瘤产生的二次谐波信号可直接观察ECM及其与癌细胞的相互作用。
10. 转移性乳腺肿瘤的血管附近有大量快速移动的巨噬细胞和其他白细胞，这些细胞可能是趋化细胞因子的来源。
11. 活体成像技术与基因表达谱分析的有效结合可为侵袭性细胞行为的相关通路提供新见解。

英文摘要：

Metastasis is the cause of death for patients with many types of cancer, but the process of tumour cell dissemination is poorly understood. As primary tumours are three-dimensional, departure of cells from primary tumours has been difficult to study. Multiphoton microscopy has been developed for in vivo imaging and, using this technique, we are beginning to understand how invasive tumour cells move.

摘要翻译： 

为何即使所有细胞均源自同一克隆，肿瘤在细胞表型及增殖潜能方面仍呈异质性？持续突变可在一定程度上解释这种差异，但似乎某些肿瘤还源于少量“癌症干细胞”，这些细胞能产生表型多样且增殖潜能较低的癌细胞。癌症干细胞可能由调控正常干细胞自我更新的基因发生突变而形成。利用这一信息，有望设计出更有效的治疗方案。

原文链接：

Intravital imaging of cell movement in tumours