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Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination

Author

Listed:
  • Caroline P. Le

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University)

  • Cameron J. Nowell

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University)

  • Corina Kim-Fuchs

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University
    University Hospital Bern)

  • Edoardo Botteri

    (European Institute of Oncology)

  • Jonathan G. Hiller

    (Peter MacCallum Cancer Centre)

  • Hilmy Ismail

    (Peter MacCallum Cancer Centre)

  • Matthew A. Pimentel

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University)

  • Ming G. Chai

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University)

  • Tara Karnezis

    (The University of Melbourne
    Tumor Angiogenesis Program, Peter MacCallum Cancer Centre)

  • Nicole Rotmensz

    (European Institute of Oncology)

  • Giuseppe Renne

    (European Institute of Oncology)

  • Sara Gandini

    (European Institute of Oncology)

  • Colin W. Pouton

    (Drug Delivery, Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University)

  • Davide Ferrari

    (The University of Melbourne)

  • Andreas Möller

    (QIMR Berghofer Medical Research Institute)

  • Steven A. Stacker

    (The University of Melbourne
    Tumor Angiogenesis Program, Peter MacCallum Cancer Centre)

  • Erica K. Sloan

    (Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University
    Peter MacCallum Cancer Centre
    Cousins Center for PNI, University of California Los Angeles
    UCLA Semel Institute, University of California Los Angeles)

Abstract

Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.

Suggested Citation

  • Caroline P. Le & Cameron J. Nowell & Corina Kim-Fuchs & Edoardo Botteri & Jonathan G. Hiller & Hilmy Ismail & Matthew A. Pimentel & Ming G. Chai & Tara Karnezis & Nicole Rotmensz & Giuseppe Renne & Sa, 2016. "Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10634
    DOI: 10.1038/ncomms10634
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    Cited by:

    1. Ling Ye & Yuanlong Hou & Wanyu Hu & Hongmei Wang & Ruopeng Yang & Qihan Zhang & Qiaoli Feng & Xiao Zheng & Guangyu Yao & Haiping Hao, 2023. "Repressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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