Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination
Identifieur interne : 001305 ( Main/Exploration ); précédent : 001304; suivant : 001306Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination
Auteurs : Caroline P. Le [Australie] ; Cameron J. Nowell [Australie] ; Corina Kim-Fuchs [Australie, Suisse] ; Edoardo Botteri [Italie] ; Jonathan G. Hiller [Australie] ; Hilmy Ismail [Australie] ; Matthew A. Pimentel [Australie] ; Ming G. Chai [Australie] ; Tara Karnezis [Australie] ; Nicole Rotmensz [Italie] ; Giuseppe Renne [Italie] ; Sara Gandini [Italie] ; Colin W. Pouton [Australie] ; Davide Ferrari [Australie] ; Andreas Möller [Australie] ; Steven A. Stacker [Australie] ; Erica K. Sloan [Australie, États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2016.
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
Url:
DOI: 10.1038/ncomms10634
PubMed: 26925549
PubMed Central: 4773495
Affiliations:
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Le</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nowell, Cameron J" sort="Nowell, Cameron J" uniqKey="Nowell C" first="Cameron J." last="Nowell">Cameron J. Nowell</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim Fuchs, Corina" sort="Kim Fuchs, Corina" uniqKey="Kim Fuchs C" first="Corina" last="Kim-Fuchs">Corina Kim-Fuchs</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Visceral Surgery and Medicine, University Hospital Bern</institution>, 3010 Bern,<country>Switzerland</country></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Botteri, Edoardo" sort="Botteri, Edoardo" uniqKey="Botteri E" first="Edoardo" last="Botteri">Edoardo Botteri</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Division of Epidemiology and Biostatistics, European Institute of Oncology</institution>, Milan 20141,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hiller, Jonathan G" sort="Hiller, Jonathan G" uniqKey="Hiller J" first="Jonathan G." last="Hiller">Jonathan G. Hiller</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Cancer Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre</institution>, East Melbourne, Victoria 3002,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ismail, Hilmy" sort="Ismail, Hilmy" uniqKey="Ismail H" first="Hilmy" last="Ismail">Hilmy Ismail</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Cancer Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre</institution>, East Melbourne, Victoria 3002,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pimentel, Matthew A" sort="Pimentel, Matthew A" uniqKey="Pimentel M" first="Matthew A." last="Pimentel">Matthew A. Pimentel</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chai, Ming G" sort="Chai, Ming G" uniqKey="Chai M" first="Ming G." last="Chai">Ming G. Chai</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Karnezis, Tara" sort="Karnezis, Tara" uniqKey="Karnezis T" first="Tara" last="Karnezis">Tara Karnezis</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Peter MacCallum Department of Oncology, The University of Melbourne</institution>, Parkville, Victoria 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Tumor Angiogenesis Program, Peter MacCallum Cancer Centre</institution>, East Melbourne, Victoria 3002,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rotmensz, Nicole" sort="Rotmensz, Nicole" uniqKey="Rotmensz N" first="Nicole" last="Rotmensz">Nicole Rotmensz</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Division of Epidemiology and Biostatistics, European Institute of Oncology</institution>, Milan 20141,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Renne, Giuseppe" sort="Renne, Giuseppe" uniqKey="Renne G" first="Giuseppe" last="Renne">Giuseppe Renne</name><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Division of Pathology and Laboratory Medicine, European Institute of Oncology</institution>, Milan 20141,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gandini, Sara" sort="Gandini, Sara" uniqKey="Gandini S" first="Sara" last="Gandini">Sara Gandini</name><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Division of Epidemiology and Biostatistics, European Institute of Oncology</institution>, Milan 20141,<country>Italy</country></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pouton, Colin W" sort="Pouton, Colin W" uniqKey="Pouton C" first="Colin W." last="Pouton">Colin W. Pouton</name><affiliation wicri:level="1"><nlm:aff id="a8"><institution>Drug Delivery, Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ferrari, Davide" sort="Ferrari, Davide" uniqKey="Ferrari D" first="Davide" last="Ferrari">Davide Ferrari</name><affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Mathematics and Statistics, The University of Melbourne</institution>, Parkville, Victoria 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Moller, Andreas" sort="Moller, Andreas" uniqKey="Moller A" first="Andreas" last="Möller">Andreas Möller</name><affiliation wicri:level="1"><nlm:aff id="a10"><institution>Cancer Division, QIMR Berghofer Medical Research Institute</institution>, Herston, Queensland 4006,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>Peter MacCallum Department of Oncology, The University of Melbourne</institution>, Parkville, Victoria 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a6"><institution>Tumor Angiogenesis Program, Peter MacCallum Cancer Centre</institution>, East Melbourne, Victoria 3002,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University</institution>, Parkville, Victoria 3052,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a4"><institution>Department of Cancer Anaesthesia and Pain Medicine, Peter MacCallum Cancer Centre</institution>, East Melbourne, Victoria 3002,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a11"><institution>Cousins Center for PNI, University of California Los Angeles</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a12"><institution>UCLA Semel Institute, University of California Los Angeles</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a13"><institution>Jonsson Comprehensive Cancer Center, University of California Los Angeles</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a14"><institution>UCLA AIDS Institute, University of California Los Angeles</institution>, Los Angeles, CA 90095,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 <italic>in vivo</italic> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Elenkov, I J" uniqKey="Elenkov I">I. J. Elenkov</name></author><author><name sortKey="Wilder, R L" uniqKey="Wilder R">R. L. Wilder</name></author><author><name sortKey="Chrousos, G P" uniqKey="Chrousos G">G. P. Chrousos</name></author><author><name sortKey="Vizi, E S" uniqKey="Vizi E">E. S. Vizi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcewen, B S" uniqKey="Mcewen B">B. S. McEwen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thaker, P H" uniqKey="Thaker P">P. H. Thaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim Fuchs, C" uniqKey="Kim Fuchs C">C. 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Le</name></noRegion><name sortKey="Chai, Ming G" sort="Chai, Ming G" uniqKey="Chai M" first="Ming G." last="Chai">Ming G. Chai</name><name sortKey="Ferrari, Davide" sort="Ferrari, Davide" uniqKey="Ferrari D" first="Davide" last="Ferrari">Davide Ferrari</name><name sortKey="Hiller, Jonathan G" sort="Hiller, Jonathan G" uniqKey="Hiller J" first="Jonathan G." last="Hiller">Jonathan G. Hiller</name><name sortKey="Ismail, Hilmy" sort="Ismail, Hilmy" uniqKey="Ismail H" first="Hilmy" last="Ismail">Hilmy Ismail</name><name sortKey="Karnezis, Tara" sort="Karnezis, Tara" uniqKey="Karnezis T" first="Tara" last="Karnezis">Tara Karnezis</name><name sortKey="Karnezis, Tara" sort="Karnezis, Tara" uniqKey="Karnezis T" first="Tara" last="Karnezis">Tara Karnezis</name><name sortKey="Kim Fuchs, Corina" sort="Kim Fuchs, Corina" uniqKey="Kim Fuchs C" first="Corina" last="Kim-Fuchs">Corina Kim-Fuchs</name><name sortKey="Moller, Andreas" sort="Moller, Andreas" uniqKey="Moller A" first="Andreas" last="Möller">Andreas Möller</name><name sortKey="Nowell, Cameron J" sort="Nowell, Cameron J" uniqKey="Nowell C" first="Cameron J." last="Nowell">Cameron J. Nowell</name><name sortKey="Pimentel, Matthew A" sort="Pimentel, Matthew A" uniqKey="Pimentel M" first="Matthew A." last="Pimentel">Matthew A. Pimentel</name><name sortKey="Pouton, Colin W" sort="Pouton, Colin W" uniqKey="Pouton C" first="Colin W." last="Pouton">Colin W. Pouton</name><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name><name sortKey="Stacker, Steven A" sort="Stacker, Steven A" uniqKey="Stacker S" first="Steven A." last="Stacker">Steven A. Stacker</name></country><country name="Suisse"><noRegion><name sortKey="Kim Fuchs, Corina" sort="Kim Fuchs, Corina" uniqKey="Kim Fuchs C" first="Corina" last="Kim-Fuchs">Corina Kim-Fuchs</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Botteri, Edoardo" sort="Botteri, Edoardo" uniqKey="Botteri E" first="Edoardo" last="Botteri">Edoardo Botteri</name></noRegion><name sortKey="Gandini, Sara" sort="Gandini, Sara" uniqKey="Gandini S" first="Sara" last="Gandini">Sara Gandini</name><name sortKey="Renne, Giuseppe" sort="Renne, Giuseppe" uniqKey="Renne G" first="Giuseppe" last="Renne">Giuseppe Renne</name><name sortKey="Rotmensz, Nicole" sort="Rotmensz, Nicole" uniqKey="Rotmensz N" first="Nicole" last="Rotmensz">Nicole Rotmensz</name></country><country name="États-Unis"><noRegion><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name></noRegion><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name><name sortKey="Sloan, Erica K" sort="Sloan, Erica K" uniqKey="Sloan E" first="Erica K." last="Sloan">Erica K. Sloan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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