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.

从早期起源开始，肿瘤细胞就与周围的正常细胞整合形成异常结构，通过血液和淋巴管甚至神经关联与宿主生物体紧密结合。利用这些连接，新出现的癌症会发送大量的介质，这些介质可以有效地扰乱整个生物体并诱导远处组织的变化。这些扰动通过促进更有利的组织环境（生态位）来支持播散性肿瘤细胞在外来组织中的持久性，从而偶然地有利于早期转移的建立。因为早期转移生态位的建立代表了转移的关键限制步骤，所以创建更合适的预处理组织会大大提高转移成功率。在这篇综述中，我们提供了迄今为止描述的原发性肿瘤机制和介质的最新观点，这些机制和介质诱导远处器官的促转移性调节，这有利于早期转移性生态位的形成。我们反思了癌症诱导的全身条件反射的性质，考虑到组织稳态的非癌症依赖性扰动也能够触发促转移性条件反射。我们认为，需要更全面地了解催化转移进展的过程，以确定预防或治疗机会。