文章：

转移的微环境调控

Microenvironmental regulation of metastasis

原文发布日期：2008-03-12

DOI: 10.1038/nrc2618

类型: Review Article

开放获取: 否

要点：

1. The tumour microenvironment has a major role in modulating the metastatic capacity of most cancers. Seminal experiments indicated that certain microenvironments can suppress malignancy. However, in most tumours these restraints are overcome such that the tumour now exploits the supporting cells to increase metastatic potential.
2. Primary and metastatic tumours cause systemic perturbations that often involve mobilizing bone marrow-derived cells that home to the tumour and promote tumour progression, malignant cell escape and survival, and growth at the secondary site.
3. Primary tumours recruit macrophages to their microenvironment and these cells increase metastatic potential by increasing tumour cell migration, invasion and intravasation. They also increase angiogenesis and thereby increase the targets for metastatic cell escape.
4. Myeloid cell-derived suppressor cells suppress immune responses to newly displayed tumour antigens and promote the metastatic potential of the tumour.
5. Mesenchymal stem cells can differentiate into many different cell types and are recruited to primary tumours where they enhance metastasis.
6. Tumour cells are protected in their travels through the circulation, particularly by platelets. These platelets together with the tumour cells activate the clotting system such that microthrombi form that help tumour cells lodge in target tissues.
7. The formation of metastases has many rate-limiting steps including survival in the distant organ, extravasation and the establishment of persistent growth. Microenvironmental cues are important at all steps and the recruitment of a variety of bone marrow-derived cells including endothelial progenitors and myeloid cell-derived cells is crucial for these processes.

要点翻译：

1. 肿瘤微环境在调节大多数癌症的转移能力中起着重要作用。开创性实验表明，某些微环境能够抑制恶性肿瘤。然而，在大多数肿瘤中这些限制机制被突破，使得肿瘤转而利用支持性细胞来增强转移潜能。
2. 原发性和转移性肿瘤会引起全身性紊乱，通常涉及动员骨髓来源的细胞，这些细胞归巢至肿瘤部位并促进肿瘤进展、恶性细胞逃逸与存活，以及在继发部位的生长。
3. 原发性肿瘤将巨噬细胞募集至其微环境中，这些细胞通过增强肿瘤细胞迁移、侵袭和内渗能力来提高转移潜能。它们还促进血管生成，从而增加转移细胞逃逸的靶点。
4. 髓系来源的抑制细胞能抑制针对新呈现肿瘤抗原的免疫反应，并提升肿瘤的转移能力。
5. 间充质干细胞可分化成多种不同细胞类型，被募集至原发性肿瘤后能增强转移过程。
6. 肿瘤细胞在循环系统迁移过程中受到保护，尤其是血小板的保护。这些血小板与肿瘤细胞共同激活凝血系统，形成微血栓帮助肿瘤细胞锚定在靶组织中。
7. 转移灶的形成包含多个限速步骤，包括在远端器官的存活、外渗和持续性生长的建立。微环境信号在所有步骤中都至关重要，而包括内皮祖细胞和髓系来源细胞在内的多种骨髓来源细胞的募集对这些过程具有关键作用。

英文摘要：

Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.

摘要翻译： 

转移是一个多阶段过程，需要癌细胞从原发肿瘤中逃逸、在循环中存活、在远处部位定植并生长。这些过程中的每一个都涉及受肿瘤微环境中非恶性细胞影响的限速步骤。这些细胞中有许多来源于骨髓，特别是髓系，它们被癌细胞招募以增强其存活、生长、侵袭和扩散。本综述描述了证明微环境在转移中作用的实验数据，指出了未来研究的领域，并提出了可能的新治疗途径。

原文链接：

Microenvironmental regulation of metastasis