Publication: Pre-metastatic niches: organ-specific homes for metastases

Thomas R. Cox, Mar 2017

Pre-metastatic niches: organ-specific homes for metastases

Our new review on the importance of the pre-metastatic niche (PMN) in cancer has just been published in Nature Reviews Cancer. It summarises the natural progression of pre-metastatic niche formation and evolution, highlighting recent advances and future hurdles.

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What is the pre-metastatic niche (PMN)?

Over 10 years ago it was shown that growing tumours are capable of inducing the formation of microenvironments in distant organs that are supportive to the survival and outgrowth of tumour cells. These microenvironments are created before the arrival of tumour cells at these sites and are were hence termed ‘pre-metastatic niches’ (PMNs).

Since then, much work has been done to uncover and define the role of pre-metastatic niches in cancer progression. Our review covers these developments including:

  • How organs of future metastasis are selectively and actively modified by the primary tumour before metastatic spread has occurred.
  • How tumours induce the formation of microenvironments in distant organs that are conducive to the survival and outgrowth of tumour cells before their arrival at these sites.
  • How PMN formation is a stepwise process resulting from the combined systemic effects of tumour-secreted factors and tumour-shed extracellular vesicles.
  • How PMN formation is initiated with local changes such as the induction of vascular leakiness, remodelling of stroma and extracellular matrix, followed by systemic effects on the immune system.
  • How the development of new technologies and approaches to identify PMNs in distant organ sites in patients could revolutionize cancer treatment and lead to pre-emptive treatments to hinder metastasis.
  • Why the PMN is a new paradigm for the initiation of metastasis.

Abstract

It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the ‘seeds’ of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the ‘soil’ at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

Links

View the abstract in PubMed
View the article on the Nature Reviews Cancer website

Citation

Peinado H et al. Pre-metastatic niches: organ-specific homes for metastases
Nature Reviews Cancer (2017) | doi:10.1038/nrc.2017.6

Key words

Cancer microenvironment, Cancer models, Metastasis, Tumour biomarkers, Tumour immunology