Letter | Published:

Neutrophils support lung colonization of metastasis-initiating breast cancer cells

Nature volume 528, pages 413417 (17 December 2015) | Download Citation

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Despite progress in the development of drugs that efficiently target cancer cells, treatments for metastatic tumours are often ineffective. The now well-established dependency of cancer cells on their microenvironment1 suggests that targeting the non-cancer-cell component of the tumour might form a basis for the development of novel therapeutic approaches. However, the as-yet poorly characterized contribution of host responses during tumour growth and metastatic progression represents a limitation to exploiting this approach. Here we identify neutrophils as the main component and driver of metastatic establishment within the (pre-)metastatic lung microenvironment in mouse breast cancer models. Neutrophils have a fundamental role in inflammatory responses and their contribution to tumorigenesis is still controversial2,3,4. Using various strategies to block neutrophil recruitment to the pre-metastatic site, we demonstrate that neutrophils specifically support metastatic initiation. Importantly, we find that neutrophil-derived leukotrienes aid the colonization of distant tissues by selectively expanding the sub-pool of cancer cells that retain high tumorigenic potential. Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis. Our results reveal the efficacy of using targeted therapy against a specific tumour microenvironment component and indicate that neutrophil Alox5 inhibition may limit metastatic progression.

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  • 21 June 2019

    In this Letter, the final two pages of the Supplementary Information, which included two tables listing primers and antibodies, respectively, were missing; see accompanying Amendment for the missing Supplementary Tables. This Letter has not been corrected online.


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We thank C. Reis e Sousa, E. Sahai, P. Scaffidi and J. Huelsken for scientific discussions, critical reading of the manuscript and sharing cell lines and mouse strains. We also thank members of the tumour-stroma interactions in cancer development (TSI) laboratory of The Crick Institute for scientific discussions, critical reading of the manuscript and practical support. We thank L. Jones for help in analysing the human breast cancer samples. We are grateful to R. Moore, E. Nye, B. Spencer-Dene and J. Bee for technical support with mice and mouse tissue. We also thank the Flow Cytometry Unit, the Bioinformatics & Biostatistics Unit and the In vivo Imaging Facility for technical assistance. We are grateful to Cancer Research UK for the funding that has allowed this work.

Author information


  1. The Francis Crick Institute, Lincolns Inn Fields Laboratories, 44 Lincolns Inn Fields, London WC2A 3LY, UK

    • Stefanie K. Wculek
    •  & Ilaria Malanchi


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S.K.W. organised and performed all experiments, helped design experiments, interpreted data and helped with manuscript preparation. I.M. conceived and supervised the study, designed experiments, interpreted the data, assisted with some aspects of the experiments and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ilaria Malanchi.

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    Supplementary Information

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    Supplementary Data

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