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

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.

SUBMITTER: Guillot J

PROVIDER: S-EPMC9007988 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Guillot Jérémy J Dominici Chloé C Lucchesi Adrien A Nguyen Huyen Thi Trang HTT Puget Angélique A Hocine Mélanie M Rangel-Sosa Martha M MM Simic Milesa M Nigri Jérémy J Guillaumond Fabienne F Bigonnet Martin M Dusetti Nelson N Perrot Jimmy J Lopez Jonathan J Etzerodt Anders A Lawrence Toby T Pudlo Pierre P Hubert Florence F Scoazec Jean-Yves JY van de Pavert Serge A SA Tomasini Richard R Chauvet Sophie S Mann Fanny F

Nature communications 20220413 1

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, mecha ...[more]

PMID: 35418199

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Dataset Information

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

Publications

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

Similar Datasets

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