肝转移灶微环境:转移中外基质的建模。

The liver metastatic niche: modelling the extracellular matrix in metastasis.

机构信息

CRUK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK.

出版信息

Dis Model Mech. 2021 Apr 1;14(4). doi: 10.1242/dmm.048801. Epub 2021 Apr 15.

Abstract

Dissemination of malignant cells from primary tumours to metastatic sites is a key step in cancer progression. Disseminated tumour cells preferentially settle in specific target organs, and the success of such metastases depends on dynamic interactions between cancer cells and the microenvironments they encounter at secondary sites. Two emerging concepts concerning the biology of metastasis are that organ-specific microenvironments influence the fate of disseminated cancer cells, and that cancer cell-extracellular matrix interactions have important roles at all stages of the metastatic cascade. The extracellular matrix is the complex and dynamic non-cellular component of tissues that provides a physical scaffold and conveys essential adhesive and paracrine signals for a tissue's function. Here, we focus on how extracellular matrix dynamics contribute to liver metastases - a common and deadly event. We discuss how matrix components of the healthy and premetastatic liver support early seeding of disseminated cancer cells, and how the matrix derived from both cancer and liver contributes to the changes in niche composition as metastasis progresses. We also highlight the technical developments that are providing new insights into the stochastic, dynamic and multifaceted roles of the liver extracellular matrix in permitting and sustaining metastasis. An understanding of the contribution of the extracellular matrix to different stages of metastasis may well pave the way to targeted and effective therapies against metastatic disease.

摘要

癌细胞从原发性肿瘤扩散到转移部位是癌症进展的关键步骤。扩散的肿瘤细胞优先在特定的靶器官中定居,这种转移的成功取决于癌细胞与它们在次级部位遇到的微环境之间的动态相互作用。关于转移生物学的两个新兴概念是,特定器官的微环境影响扩散的癌细胞的命运,以及癌细胞-细胞外基质相互作用在转移级联的所有阶段都具有重要作用。细胞外基质是组织中复杂且动态的非细胞成分,为组织提供物理支架,并传递组织功能所需的重要粘附和旁分泌信号。在这里,我们重点关注细胞外基质动力学如何促进肝转移——这是一种常见且致命的事件。我们讨论了健康和前转移肝脏的基质成分如何支持扩散的癌细胞的早期播种,以及来自癌症和肝脏的基质如何促进随着转移进展而发生的小生境组成的变化。我们还强调了提供新见解的技术发展,这些见解涉及肝脏细胞外基质在允许和维持转移中的随机、动态和多方面作用。对细胞外基质在转移不同阶段的贡献的理解可能为针对转移性疾病的靶向和有效治疗铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0235/8077555/16bbc06be8a3/dmm-14-048801-g1.jpg

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