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

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, Sara Gandini, Colin W. Pouton, Davide Ferrari, Andreas Möller, Steven A. Stacker, Erica K. Sloan

Research output: Contribution to journalArticleResearchpeer-review

70 Citations (Scopus)

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.

Original languageEnglish
Article number10634
Number of pages14
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 1 Mar 2016

Cite this

Le, Caroline P. ; Nowell, Cameron J. ; Kim-Fuchs, Corina ; Botteri, Edoardo ; Hiller, Jonathan G. ; Ismail, Hilmy ; Pimentel, Matthew A. ; Chai, Ming G. ; Karnezis, Tara ; Rotmensz, Nicole ; Renne, Giuseppe ; Gandini, Sara ; Pouton, Colin W. ; Ferrari, Davide ; Möller, Andreas ; Stacker, Steven A. ; Sloan, Erica K. / Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. In: Nature Communications. 2016 ; Vol. 7.
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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.",
author = "Le, {Caroline P.} and Nowell, {Cameron J.} and Corina Kim-Fuchs and Edoardo Botteri and Hiller, {Jonathan G.} and Hilmy Ismail and Pimentel, {Matthew A.} and Chai, {Ming G.} and Tara Karnezis and Nicole Rotmensz and Giuseppe Renne and Sara Gandini and Pouton, {Colin W.} and Davide Ferrari and Andreas M{\"o}ller and Stacker, {Steven A.} and Sloan, {Erica K.}",
year = "2016",
month = "3",
day = "1",
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Le, CP, Nowell, CJ, Kim-Fuchs, C, Botteri, E, Hiller, JG, Ismail, H, Pimentel, MA, Chai, MG, Karnezis, T, Rotmensz, N, Renne, G, Gandini, S, Pouton, CW, Ferrari, D, Möller, A, Stacker, SA & Sloan, EK 2016, 'Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination', Nature Communications, vol. 7, 10634. https://doi.org/10.1038/ncomms10634

Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. / Le, Caroline P.; Nowell, Cameron J.; Kim-Fuchs, Corina; Botteri, Edoardo; Hiller, Jonathan G.; Ismail, Hilmy; Pimentel, Matthew A.; Chai, Ming G.; Karnezis, Tara; Rotmensz, Nicole; Renne, Giuseppe; Gandini, Sara; Pouton, Colin W.; Ferrari, Davide; Möller, Andreas; Stacker, Steven A.; Sloan, Erica K.

In: Nature Communications, Vol. 7, 10634, 01.03.2016.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Le, Caroline P.

AU - Nowell, Cameron J.

AU - Kim-Fuchs, Corina

AU - Botteri, Edoardo

AU - Hiller, Jonathan G.

AU - Ismail, Hilmy

AU - Pimentel, Matthew A.

AU - Chai, Ming G.

AU - Karnezis, Tara

AU - Rotmensz, Nicole

AU - Renne, Giuseppe

AU - Gandini, Sara

AU - Pouton, Colin W.

AU - Ferrari, Davide

AU - Möller, Andreas

AU - Stacker, Steven A.

AU - Sloan, Erica K.

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