Small extracellular vesicles containing miR-192/215 mediate hypoxia-induced cancer-associated fibroblast development in head and neck squamous cell carcinoma.
Cancer Lett
; 506: 11-22, 2021 05 28.
Article
en En
| MEDLINE
| ID: mdl-33639203
ABSTRACT
The mechanisms underlying the hypoxic cancer cell-mediated differentiation of cancer-associated fibroblasts (CAFs) have not been elucidated yet. The present study showed that the hypoxic head and neck squamous cell carcinoma (HNSCC) cells promoted CAF-like differentiation through secreting TGF-ß and small extracellular vesicles (sEVs) that contain enhanced levels of miR-192/215 family miRNAs. Caveolin-1 (CAV1), which is a target gene of miR-192/215, inhibited the TGF-ß/SMAD signaling and promoted CAF-like differentiation of the fibroblasts. Restoring the levels of CAV1 inhibited the hypoxic sEV- and TGF-ß-induced CAF-like differentiation. The enhanced levels of miR-192/215 encapsulated in the HNSCC tissue-derived sEVs (but not serum-derived sEVs) indicated hypoxic and aggressive cancer stroma. miR-215 in the tumor tissue-derived sEVs (but not circulating sEVs) was correlated with poor overall survival of patients with HNSCC. This study demonstrated that sEVs function as a "courier" to deliver miRNAs from the cancer cells to the fibroblasts, which promotes the remodeling of the hypoxic tumor microenvironment, and that cancer tissue-derived sEV could potentially serve as a source of biomarker.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Vesículas Extracelulares
/
Fibroblastos Asociados al Cáncer
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Hipoxia Tumoral
/
Carcinoma de Células Escamosas de Cabeza y Cuello
/
Neoplasias de Cabeza y Cuello
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2021
Tipo del documento:
Article