文章：

转移：一个生死攸关的问题

Metastasis: a question of life or death

原文发布日期：2006-06-01

DOI: 10.1038/nrc1886

类型: Review Article

开放获取: 否

要点：

1. Metastasis occurs through a series of sequential steps in which tumour cells first migrate from the primary tumour, penetrate blood vessels and then colonize distant sites. It is a highly inefficient process. Indeed, very few of the tumour cells that gain access to the vasculature give rise to metastastic foci in a secondary organ.
2. Recent data indicate that the mechanisms controlling metastasis can be regulated independently from primary tumour development.
3. In vitro and in vivo, the metastatic potential of tumours is associated with an increased resistance to apoptosis. Furthermore, the experimental modulation of apoptotic or anti-apoptotic factors influences metastatic efficiency.
4. Anoikis and amorphosis are important barriers to metastasis. Anoikis is cell death induced by the disruption of cell attachment and cell–matrix interactions, whereas amorphosis is cell death stimulated by the loss of cytoskeletal architecture.
5. Early survival of tumour cells after attachment to the secondary site and the development of micrometastases are crucial steps of the metastatic process.
6. Metastasis is the most common cause of cancer death. Most patients with metastatic disease respond transiently to conventional treatments. Further elucidation of the relationship between resistance to apoptosis of metastatic cancer cells and their chemoresistance should provide important clues to improve systemic therapies.

要点翻译：

1. 转移通过一系列连续步骤发生：肿瘤细胞首先从原发肿瘤迁移，穿透血管，然后在远处定植。这是一个效率极低的过程。实际上，能够进入血管系统的肿瘤细胞中，仅有极少数能在次级器官中形成转移灶。
2. 最新数据表明，控制转移的机制可能独立于原发肿瘤的发展而受到调控。
3. 在体外和体内实验中，肿瘤的转移潜能与细胞凋亡抵抗性增强相关。此外，对促凋亡或抗凋亡因子的实验性调控会影响转移效率。
4. 失巢凋亡和形态凋亡是转移的重要屏障。失巢凋亡是由细胞附着和细胞-基质相互作用破坏诱导的细胞死亡，而形态凋亡则是由细胞骨架结构丧失刺激引发的细胞死亡。
5. 肿瘤细胞附着于次级部位后的早期存活以及微转移灶的形成是转移过程的关键步骤。
6. 转移是癌症最常见的致死原因。大多数转移性疾病患者对常规治疗仅产生短暂反应。进一步阐明转移性癌细胞凋亡抗性与其化疗耐药性之间的关系，将为改善全身性治疗方案提供重要线索。

英文摘要：

The metastatic process is highly inefficient — very few of the many cells that migrate from the primary tumour successfully colonize distant sites. One proposed mechanism to explain this inefficiency is provided by the cancer stem cell model, which hypothesizes that micrometastases can only be established by tumour stem cells, which are few in number. However, recent in vitro and in vivo observations indicate that apoptosis is an important process regulating metastasis. Here we stress that the inhibition of cell death, apart from its extensively described function in primary tumour development, is a crucial characteristic of metastatic cancer cells.

摘要翻译： 

转移过程效率极低——从原发瘤迁出的众多细胞中，仅有极少数能在远端成功定植。癌症干细胞模型为这种低效性提出了一种解释机制：该模型假设只有数量稀少的肿瘤干细胞才能建立微转移灶。然而，近期的体外与体内观察表明，细胞凋亡是调控转移的重要过程。在此我们强调，抑制细胞死亡不仅是原发瘤发展中被广泛描述的功能，更是转移性癌细胞的关键特征。

原文链接：

Metastasis: a question of life or death