Cancer and Metastasis Reviews

, Volume 32, Issue 3–4, pp 449–464 | Cite as

The pre-metastatic niche: finding common ground

  • Jaclyn Sceneay
  • Mark J. SmythEmail author
  • Andreas MöllerEmail author


It is rapidly becoming evident that the formation of tumor-promoting pre-metastatic niches in secondary organs adds a previously unrecognized degree of complexity to the challenge of curing metastatic disease. Primary tumor cells orchestrate pre-metastatic niche formation through secretion of a variety of cytokines and growth factors that promote mobilization and recruitment of bone marrow-derived cells to future metastatic sites. Hypoxia within the primary tumor, and secretion of specific microvesicles termed exosomes, are emerging as important processes and vehicles for tumor-derived factors to modulate pre-metastatic sites. It has also come to light that reduced immune surveillance is a novel mechanism through which primary tumors create favorable niches in secondary organs. This review provides an overview of our current understanding of underlying mechanisms of pre-metastatic niche formation and highlights the common links as well as discrepancies between independent studies. Furthermore, the possible clinical implications, links to metastatic persistence and dormancy, and novel approaches for treatment of metastatic disease through reversal of pre-metastatic niche formation are identified and explored.


Pre-metastatic niche Hypoxia Immunosuppression Myeloid-derived suppressor cells Exosomes Tumor dormancy 



The authors would like to thank the members of the Möller and Smyth groups for valuable suggestions for the review. The authors acknowledge the generous support of a State Trustees Australia Foundation scholarship to JS; National Health and Medical Research Council (NH&MRC) Australia Fellowship, NH&MRC Program Grant, and Victorian Cancer Agency support to MJS; and an Association of International Cancer Research Project Grant and a National Breast Cancer Foundation Fellowship to AM.

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Cancer Genomics and Genetics LaboratoryPeter MacCallum Cancer CentreEast MelbourneAustralia
  2. 2.Department of PathologyThe University of MelbourneParkvilleAustralia
  3. 3.Tumour Microenvironment LaboratoryQueensland Institute of Medical ResearchHerstonAustralia
  4. 4.Cancer Immunology ProgramPeter MacCallum Cancer CentreEast MelbourneAustralia
  5. 5.Sir Peter MacCallum Department of OncologyThe University of MelbourneParkvilleAustralia
  6. 6.Immunology in Cancer and Infection LaboratoryQueensland Institute of Medical ResearchHerstonAustralia

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