Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain.
Sci Adv
; 8(40): eabn5535, 2022 10 07.
Article
en En
| MEDLINE
| ID: mdl-36206343
ABSTRACT
Tumor innervation is a common phenomenon with unknown mechanism. Here, we discovered a direct mechanism of tumor-associated macrophage (TAM) for promoting de novo neurogenesis via a subset showing neuronal phenotypes and pain receptor expression associated with cancer-driven nocifensive behaviors. This subset is rich in lung adenocarcinoma associated with poorer prognosis. By elucidating the transcriptome dynamics of TAM with single-cell resolution, we discovered a phenomenon "macrophage to neuron-like cell transition" (MNT) for directly promoting tumoral neurogenesis, evidenced by macrophage depletion and fate-mapping study in lung carcinoma models. Encouragingly, we detected neuronal phenotypes and activities of the bone marrow-derived MNT cells (MNTs) in vitro. Adoptive transfer of MNTs into NOD/SCID mice markedly enhanced their cancer-associated nocifensive behaviors. We identified macrophage-specific Smad3 as a pivotal regulator for promoting MNT at the genomic level; its disruption effectively blocked the tumor innervation and cancer-dependent nocifensive behaviors in vivo. Thus, MNT may represent a precision therapeutic target for cancer pain.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor en Cáncer
/
Neoplasias Pulmonares
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2022
Tipo del documento:
Article