Abstract

Organ-specific metastasis to secondary organs is dependent on the formation of a supportive pre-metastatic niche. This tissue-specific microenvironmental response is thought to be mediated by mutational and epigenetic changes to primary tumour cells resulting in altered cross-talk between cell types. This response is augmented through the release of tumour and stromal signalling mediators including cytokines, chemokines, exosomes and growth factors. Although researchers have elucidated some of the cancer-promoting features that are bespoke to organotropic metastasis to the lungs, it remains unclear if these are organ-specific or generic between organs. Understanding the mechanisms that mediate the metastasis-promoting synergy between the host microenvironment, immunity, and pulmonary structures may elucidate predictive, prognostic and therapeutic markers that could be targeted to reduce the metastatic burden of disease. Herein, we give an updated summary of the known cellular and molecular mechanisms that contribute to the formation of the lung pre-metastatic niche and tissue-specific metastasis.

摘要

器官特异性转移到次级器官取决于支持性转移前生态位的形成。这种组织特异性微环境反应被认为是由原发性肿瘤细胞的突变和表观遗传变化介导的，导致细胞类型之间的串扰改变。这种反应通过释放肿瘤和基质信号介质（包括细胞因子、趋化因子、外泌体和生长因子）来增强。尽管研究人员已经阐明了一些与器官向肺部转移有关的促癌特征，但尚不清楚这些特征是器官特异性的还是器官之间的通用特征。了解介导宿主微环境、免疫和肺结构之间促进转移的协同作用的机制可以阐明预测、可以针对减少疾病转移负担的预后和治疗标志物。在此，我们对有助于形成肺转移前生态位和组织特异性转移的已知细胞和分子机制进行了更新总结。