Ursini-Siegel Josie, Siegel Peter M
Lady Davis Institute for Medical Research, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Oncology, McGill University, Montreal, Quebec, Canada.
Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Oncology, McGill University, Montreal, Quebec, Canada; Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada; Department of Biochemistry, McGill University, Montreal, Quebec, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Cancer Lett. 2016 Sep 28;380(1):281-8. doi: 10.1016/j.canlet.2015.11.009. Epub 2015 Nov 11.
The emergence of metastatic disease constitutes a significant life-threatening development during cancer progression. To date, intensive efforts have been focused on understanding the intrinsic properties that confer malignant potential to cancer cells, as well as the role of the primary tumour microenvironment in promoting cancer metastasis. Beyond events occurring at the primary site, the metastatic cascade is composed of numerous barriers that must be overcome in order for disseminating cancer cells to form distal metastases. The most formidable of these is the ability of cancer cells to seed and grow in a completely foreign microenvironment. Interestingly, solid malignancies often display a particular tropism for specific tissue sites. For example, breast patients with metastatic disease will often develop bone, lung, liver or brain metastases. This mini-review will explore aspects of pre-existing and induced metastatic niches and focus on how the unique composition and function of diverse niche components, within common sites of breast cancer metastasis, enable the survival and growth of disseminated cancer cells. These common supportive functions of the niche are provided by a complex array of stromal components and molecular mechanisms that are, in part, reflective of the tissue in which the metastases arise. Finally, the metastatic niche is a dynamic structure that is continually altered and sculpted by the cancer cells during progression of the metastatic lesion.
转移性疾病的出现是癌症进展过程中严重威胁生命的一个阶段。迄今为止，人们一直致力于了解赋予癌细胞恶性潜能的内在特性，以及原发性肿瘤微环境在促进癌症转移中的作用。除了原发部位发生的事件外，转移级联反应还包括许多障碍，癌细胞要形成远处转移就必须克服这些障碍。其中最严峻的挑战是癌细胞在完全陌生的微环境中着床和生长的能力。有趣的是，实体恶性肿瘤通常对特定组织部位表现出特殊的嗜性。例如，患有转移性疾病的乳腺癌患者常常会发生骨、肺、肝或脑转移。这篇综述将探讨预先存在的和诱导产生的转移小生境的各个方面，并重点关注乳腺癌转移常见部位内不同小生境成分的独特组成和功能如何使播散的癌细胞得以存活和生长。小生境的这些常见支持功能由一系列复杂的基质成分和分子机制提供，这些成分和机制部分反映了转移灶所在的组织。最后，转移小生境是一个动态结构，在转移病灶进展过程中会不断被癌细胞改变和塑造。
