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Nat Commun ; 13(1): 1985, 2022 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-35418199

RESUMEN

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.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animales , Macrófagos , Ratones , Sistema Nervioso Simpático/fisiología , Microambiente Tumoral , Neoplasias Pancreáticas
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