Fractionated irradiation induces radioresistant oral carcinoma cells with enhanced malignant phenotypes.
Arch Oral Biol
; 164: 105988, 2024 Aug.
Article
de En
| MEDLINE
| ID: mdl-38788293
ABSTRACT
OBJECTIVE:
The fact that certain oral carcinoma patients experience radiotherapy failure implies that a more radioresistant and aggressive phenotype of surviving cancer cells potentially occurs during treatment. Our study aimed to establish radioresistant oral cancer cells through a fractionated irradiation protocol that mimics clinically relevant radiotherapy dosing strategies and to investigate all-round alterations in the malignant phenotype.METHODS:
Radioresistant oral carcinoma cells were generated by exposing Cal27 and Detroit 562 cells to 60 Gy radiation in 10 dose-escalating fractions and verified by cell immunofluorescence. Specific markers related to the epithelial-mesenchymal transition (EMT) process and the cancer stem cell (CSC) phenotype were assessed by Western blotting. Cell invasion and migration were evaluated using Matrigel-coated transwell and wound healing assays, respectively. Nontargeted metabolomics was used to mechanistically delineate the potential metabolic patterns linked to EMT and CSCs; the CSC phenotype was also examined by sphere formation assays and cell immunofluorescence.RESULTS:
Radioresistant oral carcinoma cell lines were successfully established and validated. These cells exhibited enhanced EMT and increase in both cell invasion and migration. These radioresistant cells further demonstrated a high metabolic profile, notably marked by lipid metabolism reprogramming and functional enrichment of ATP-binding cassette (ABC) transporters. Consistently, enhanced CSC phenotype in radioresistant cells was confirmed by elevated expression of stemness markers and increased sphere-forming capacity.CONCLUSION:
Radioresistant oral carcinoma cells subjected to fractionated radiation exhibit an augmented malignant phenotype. The metabolic characteristics linked to enhanced EMT and CSC phenotypes provide potential targets for improving radiotherapy in oral carcinoma.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Phénotype
/
Radiotolérance
/
Cellules souches tumorales
/
Tumeurs de la bouche
/
Mouvement cellulaire
/
Fractionnement de la dose d'irradiation
/
Transition épithélio-mésenchymateuse
Limites:
Humans
Langue:
En
Journal:
Arch Oral Biol
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Royaume-Uni