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Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer

Author

Listed:
  • Jérémy Guillot

    (Aix Marseille Univ, CNRS, IBDM)

  • Chloé Dominici

    (Aix Marseille Univ, CNRS, IBDM)

  • Adrien Lucchesi

    (Aix Marseille Univ, CNRS, IBDM)

  • Huyen Thi Trang Nguyen

    (Aix Marseille Univ, CNRS, IBDM
    University of Science and Technology of Hanoi (USTH), VAST)

  • Angélique Puget

    (Aix Marseille Univ, CNRS, IBDM)

  • Mélanie Hocine

    (Aix Marseille Univ, CNRS, IBDM)

  • Martha M. Rangel-Sosa

    (Aix Marseille Univ, CNRS, IBDM)

  • Milesa Simic

    (Aix Marseille Univ, CNRS, INSERM, CIML)

  • Jérémy Nigri

    (Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM)

  • Fabienne Guillaumond

    (Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM)

  • Martin Bigonnet

    (Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM)

  • Nelson Dusetti

    (Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM)

  • Jimmy Perrot

    (Lyon Sud University Hospital, Hospices Civils de Lyon)

  • Jonathan Lopez

    (Lyon Sud University Hospital, Hospices Civils de Lyon
    Lyon 1 University, Université de Lyon
    Cancer Research Center of Lyon, INSERM U1052, CNRS UMR5286)

  • Anders Etzerodt

    (Aix Marseille Univ, CNRS, INSERM, CIML
    Aarhus University)

  • Toby Lawrence

    (Aix Marseille Univ, CNRS, INSERM, CIML)

  • Pierre Pudlo

    (Aix Marseille Univ, CNRS, Centrale Marseille, I2M)

  • Florence Hubert

    (Aix Marseille Univ, CNRS, Centrale Marseille, I2M)

  • Jean-Yves Scoazec

    (Gustave Roussy Cancer Campus)

  • Serge A. Pavert

    (Aix Marseille Univ, CNRS, INSERM, CIML)

  • Richard Tomasini

    (Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM)

  • Sophie Chauvet

    (Aix Marseille Univ, CNRS, IBDM)

  • Fanny Mann

    (Aix Marseille Univ, CNRS, IBDM)

Abstract

Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment of pre-existing sympathetic nerves within tumors plus an active, localized sprouting of axon terminals into non-neoplastic lesions and tumor periphery. Ablation of the innervating sympathetic nerves increases tumor growth and spread. This effect is explained by the observation that sympathectomy increases intratumoral CD163+ macrophage numbers, which contribute to the worse outcome. Altogether, our findings provide insights into the mechanisms by which the sympathetic nervous system exerts cancer-protective properties in a mouse model of PDAC.

Suggested Citation

  • Jérémy Guillot & Chloé Dominici & Adrien Lucchesi & Huyen Thi Trang Nguyen & Angélique Puget & Mélanie Hocine & Martha M. Rangel-Sosa & Milesa Simic & Jérémy Nigri & Fabienne Guillaumond & Martin Bigo, 2022. "Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29659-w
    DOI: 10.1038/s41467-022-29659-w
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    References listed on IDEAS

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    1. Andrew V. Biankin & Nicola Waddell & Karin S. Kassahn & Marie-Claude Gingras & Lakshmi B. Muthuswamy & Amber L. Johns & David K. Miller & Peter J. Wilson & Ann-Marie Patch & Jianmin Wu & David K. Chan, 2012. "Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes," Nature, Nature, vol. 491(7424), pages 399-405, November.
    2. Philippe Mauffrey & Nicolas Tchitchek & Vilma Barroca & Alexis-Pierre Bemelmans & Virginie Firlej & Yves Allory & Paul-Henri Roméo & Claire Magnon, 2019. "Progenitors from the central nervous system drive neurogenesis in cancer," Nature, Nature, vol. 569(7758), pages 672-678, May.
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