Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell
Autor: | Ruoyu Wang, Longyu Cai, Qiuge Liu, Zhi Wang, Shanshan Liang, Heming Li, Piao Wang |
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Rok vydání: | 2020 |
Předmět: |
Cancer Research
biology business.industry Cell medicine.disease migration radioresistance epithelial-mesenchymal transition (EMT) medicine.anatomical_structure Oncology Nasopharyngeal carcinoma Downregulation and upregulation Nasopharyngeal carcinoma (NPC) PD-L1 biology.protein Cancer research programmed cell death ligand 1 (PD-L1) Medicine Radiology Nuclear Medicine and imaging Original Article Epithelial–mesenchymal transition business |
Zdroj: | Translational Cancer Research |
ISSN: | 2219-6803 |
Popis: | Background The acquisition of radioresistance by nasopharyngeal carcinoma (NPC) cells during radiotherapy may lead to tumor metastasis and poor survival. This study aimed to explore the mechanism of long-term radiation-induced NPC metastasis. Methods The radioresistant NPC cell, Hone-1R, was established for further study. A colony-forming assay was selected for the evaluation of radioresistant capacity, while a scratch wound healing assay was used to detect tumor cell migration. The expression of relative protein levels were detected by Western blot (WB) analysis and immunofluorescence. Cell morphology was acquired by microscopy. The programmed cell death ligand-1 (PD-L1) expression level in NPC tumor tissues was evaluated based on the publicly available datasets of NPC patients. Results A radioresistant NPC cell, Hone-1R, was established with a total dose of 180 Gy, and verified by radioresistant capacity testing. The morphology of Hone-1R cells showed obvious mesenchymal-like cells. WB and wound healing assays indicated that Hone-1R cells exhibited an epithelial-mesenchymal transition (EMT) phenotype with high migration ability and upregulation of PD-L1. Knockdown of PD-L1 reversed EMT status and reduced the migration ability of Hone-1R cells. Further analysis indicated that PD-L1 was overexpressed in more advanced stages and was positively correlated with the EMT score in NPC patients based on in silico analysis. Conclusions Our study revealed that long-term radiation induces EMT and increases migration ability of NPC radioresistant cells through upregulation of PD-L1. These results advance our investigation of the underlying mechanism of ionizing radiation (IR)-induced migration, and suggest potential interventions to reverse EMT-induced acquisition of radioresistance in NPC. |
Databáze: | OpenAIRE |
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