Secreted clusterin inhibits tumorigenesis by modulating tumor cells and macrophages in human meningioma.
Neuro Oncol
; 26(7): 1262-1279, 2024 Jul 05.
Article
en En
| MEDLINE
| ID: mdl-38416702
ABSTRACT
BACKGROUND:
Meningioma is the most common primary intracranial tumor with a high frequency of postoperative recurrence, yet the biology of the meningioma malignancy process is still obscure.METHODS:
To identify potential therapeutic targets and tumor suppressors, we performed single-cell transcriptome analysis through meningioma malignancy, which included 18 samples spanning normal meninges, benign and high-grade in situ tumors, and lung metastases, for extensive transcriptome characterization. Tumor suppressor candidate gene and molecular mechanism were functionally validated at the animal model and cellular levels.RESULTS:
Comprehensive analysis and validation in mice and clinical cohorts indicated clusterin (CLU) had suppressive function for meningioma tumorigenesis and malignancy by inducing mitochondria damage and triggering type 1 interferon pathway dependent on its secreted isoform, and the inhibition effect was enhanced by TNFα as TNFα also induced type 1 interferon pathway. Meanwhile, both intra- and extracellular CLU overexpression enhanced macrophage polarization towards M1 phenotype and TNFα production, thus promoting tumor killing and phagocytosis.CONCLUSIONS:
CLU might be a key brake of meningioma malignance by synchronously modulating tumor cells and their microenvironment. Our work provides comprehensive insights into meningioma malignancy and a potential therapeutic strategy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Clusterina
/
Macrófagos
/
Neoplasias Meníngeas
/
Meningioma
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuro Oncol
Asunto de la revista:
NEOPLASIAS
/
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China