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肿瘤转移的当前和新兴概念。

Current and emerging concepts in tumour metastasis.

机构信息

Department of Pathology, University of Aberdeen Medical Buildings, Foresterhill, Aberdeen AB25 2ZD, UK.

出版信息

J Pathol. 2010 Sep;222(1):1-15. doi: 10.1002/path.2727.

Abstract

Disseminated cancer accounts for most deaths due to malignancy. Despite this, research has focused predominantly on tumour development and progression at the primary site. Recently, attention has shifted towards the field of tumour metastasis. Several new and exciting concepts that have emerged in the past few years may shed light on this complex area. The established canonical theory of tumour metastasis, as a process emerging from a stepwise accumulation of genetic events fuelled by clonal evolution, has been challenged. New evidence suggests that malignant cells can disseminate at a much earlier stage than previously recognized in tumourigenesis. These findings have direct relevance to clinical practice and shed new light on tumour biology. Gene-profiling studies support this theory, suggesting that metastatic ability may be an innate property shared by the bulk of cells present early in a developing tumour mass. There is a growing recognition of the importance of host factors outside the primary site in the development of metastatic disease. The role of the 'pre-metastatic niche' is being defined and with this comes a new understanding of the function of bone marrow-derived progenitor cells in directing the dissemination of malignant cells to distant sites. Current research has highlighted the crucial roles played by non-neoplastic host cells within the tumour microenvironment in regulating metastasis. These new concepts have wide-ranging implications for our overall understanding of tumour metastasis and for the development of cancer therapeutics.

摘要

转移性癌症是大多数恶性肿瘤死亡的原因。尽管如此,研究主要集中在原发性肿瘤的发展和进展上。最近,人们的注意力转向了肿瘤转移领域。在过去的几年中出现了一些新的令人兴奋的概念,可能为这一复杂领域提供了一些启示。经典的肿瘤转移理论认为,肿瘤转移是一个逐步积累遗传事件的过程,这些事件是由克隆进化驱动的,但这一理论受到了挑战。新的证据表明,恶性细胞可以在肿瘤发生的早期阶段更早地扩散。这些发现与临床实践直接相关,为肿瘤生物学提供了新的见解。基因谱研究支持这一理论,表明转移能力可能是早期肿瘤块中大部分细胞所具有的固有特性。人们越来越认识到原发性肿瘤以外的宿主因素在转移性疾病发展中的重要性。正在定义“前转移生态位”的作用,这也带来了对骨髓源性祖细胞在指导恶性细胞向远处扩散中的作用的新认识。目前的研究强调了肿瘤微环境中非肿瘤宿主细胞在调节转移中的关键作用。这些新概念对我们全面理解肿瘤转移和癌症治疗的发展具有广泛的影响。

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