癌症引起的远端器官系统性预条件：为转移细胞构建“生态位”
Cancer-induced systemic pre-conditioning of distant organs: building a niche for metastatic cells
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影响因子:66.8
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Dec
作者:
Nicolas Rabas, Rute M M Ferreira, Stefania Di Blasio, Ilaria Malanchi
DOI:
10.1038/s41568-024-00752-0
摘要
从早期起，肿瘤细胞与周围正常细胞融合，形成异常结构，通过血管、淋巴管甚至神经系统与宿主体紧密连接。利用这些连接，新兴癌症会释放大量介质，有效干扰整个机体，诱导远端组织的变化。这些扰动偶然促成早期转移的建立，通过促进更有利的组织环境（生态位），支持弥散肿瘤细胞在异物组织中的存活。由于早期转移生态位的建立是转移的关键限制步骤，创建更适宜的预条件组织极大增强了转移成功率。在本综述中，我们更新了迄今所描述的促转移性远端器官预条件机制和介质，强调这些机制有助于早期生态位形成。我们反思癌症引起的系统性预条件的本质，认为非癌症依赖的组织稳态扰动也能触发促转移条件。我们认为需要一个更全面的视角来理解推动转移进程的机制，从而发现预防或治疗的潜在机会。
Abstract
From their early genesis, tumour cells integrate with the surrounding normal cells to form an abnormal structure that is tightly integrated with the host organism via blood and lymphatic vessels and even neural associations. Using these connections, emerging cancers send a plethora of mediators that efficiently perturb the entire organism and induce changes in distant tissues. These perturbations serendipitously favour early metastatic establishment by promoting a more favourable tissue environment (niche) that supports the persistence of disseminated tumour cells within a foreign tissue. Because the establishment of early metastatic niches represents a key limiting step for metastasis, the creation of a more suitable pre-conditioned tissue strongly enhances metastatic success. In this Review, we provide an updated view of the mechanisms and mediators of primary tumours described so far that induce a pro-metastatic conditioning of distant organs, which favours early metastatic niche formation. We reflect on the nature of cancer-induced systemic conditioning, considering that non-cancer-dependent perturbations of tissue homeostasis are also able to trigger pro-metastatic conditioning. We argue that a more holistic view of the processes catalysing metastatic progression is needed to identify preventive or therapeutic opportunities.