文章：

癌细胞在转移部位的播散和生长

Dissemination and growth of cancer cells in metastatic sites

原文发布日期：2002-08-01

DOI: 10.1038/nrc865

类型: Review Article

开放获取: 否

要点：

1. Metastasis consists of a series of sequential steps, all of which must be successfully completed. These include shedding of cells from a primary tumour into the circulation, survival of the cells in the circulation, arrest in a new organ, extravasation into the surrounding tissue, initiation and maintenance of growth, and vascularization of the metastatic tumour.
2. Some types of tumour show an organ-specific pattern of metastasis. Both 'seed' (the cancer cell) and 'soil' (factors in the organ environment) contribute to this organ specificity.
3. Mechanical factors influence the initial fate of cancer cells after they have left a primary tumour. Blood-flow patterns from the primary tumour determine which organ the cells travel to first. There, the relative sizes of cancer cells and capillaries lead to the efficient arrest of most circulating cancer cells in the first capillary bed that they encounter.
4. After cells have arrested in an organ, their ability to grow is dictated by molecular interactions of the cells with the environment in the organ.
5. Metastasis is an inefficient process. In vivo videomicroscopy and cell-fate analysis have led to the conclusion that early steps in metastasis are completed very efficiently. By contrast, later steps in the process are inefficient. Metastatic inefficiency is due primarily to the regulation of cancer-cell growth in secondary sites.
6. Metastases can occur many years after primary cancer treatment. Tumour dormancy might be due to pre-angiogenic micrometastases that subsequently acquire the ability to become vascularized, or solitary cells that persist for an extended period of time without division in a secondary site. These cells would be resistant to current cancer therapies that target actively dividing cells.
7. Because growth of metastases is a primary determinant of metastatic outcome, the growth phase of the metastatic process is a promising therapeutic target. Treatments that target the specific 'seed–soil' compatibility that results in organ-specific metastatic growth would be especially useful.

要点翻译：

1. 转移由一系列连续步骤构成，所有步骤都必须成功完成。这些步骤包括：从原发肿瘤脱落进入循环系统的细胞、在循环中的存活、在新器官中的滞留、向周围组织的浸润、转移灶生长的启动与维持以及转移瘤的血管化。
2. 某些肿瘤类型表现出器官特异性转移模式。这种器官特异性既取决于"种子"（癌细胞）也取决于"土壤"（器官微环境中的因子）。
3. 机械因素会影响癌细胞离开原发肿瘤后的初始命运。从原发肿瘤流出的血流模式决定了细胞首先到达的器官。在该器官中，癌细胞与毛细血管的相对大小导致大多数循环癌细胞在首次遇到的毛细血管床中被有效截留。
4. 细胞在器官中滞留后，其生长能力取决于细胞与器官微环境的分子相互作用。
5. 转移是一个低效的过程。体内显微成像技术和细胞命运分析表明：转移的早期步骤完成效率很高，而后期步骤则效率低下。转移低效主要源于次级部位对癌细胞生长的调控。
6. 转移可发生在原发性癌症治疗多年后。肿瘤休眠可能是由于血管化前微转移灶随后获得血管化能力，或是由于孤立细胞在次级部位长期存留而不分裂。这些细胞对当前针对活跃分裂细胞的癌症疗法具有耐药性。
7. 由于转移灶的生长是转移结局的主要决定因素，转移过程的生长阶段是很有前景的治疗靶点。针对导致器官特异性转移生长的特定"种子-土壤"相容性的治疗方法将具有特殊价值。

英文摘要：

Metastases, rather than primary tumours, are responsible for most cancer deaths. To prevent these deaths, improved ways to treat metastatic disease are needed. Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cells will grow there. Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy.

摘要翻译： 

转移瘤，而非原发肿瘤，是导致大多数癌症死亡的原因。为了防止这些死亡，需要改进治疗转移性疾病的方法。血流和其他机械因素会影响癌细胞向特定器官的输送，而癌细胞与新器官之间的分子相互作用则会影响细胞在该处生长的概率。抑制继发部位转移瘤的生长为癌症治疗提供了一种有前景的途径。

原文链接：

Dissemination and growth of cancer cells in metastatic sites