Cisplatin‐induced programmed cell death ligand‐2 expression is associated with metastasis ability in oral squamous cell carcinoma

Autor: Hiroshi Kajiya, Koji Okabe, Mina Sasaki, Jun Ohno, Shinji Okano, Tetsuro Ikebe, Shunichi Sudo, Akimitsu Hiraki, Yuri Katsumata
Rok vydání: 2020
Předmět:
Male
STAT3 Transcription Factor
0301 basic medicine
Cancer Research
Programmed cell death
Cell
cisplatin
signal transducers and activator of transcription 1/3
Biology
Metastasis
03 medical and health sciences
Basic and Clinical Immunology
0302 clinical medicine
Cell Line
Tumor
medicine
metastasis
Humans
Neoplasm Invasiveness
STAT1
Neoplasm Metastasis
Cell Proliferation
Cisplatin
Tissue microarray
Original Articles
General Medicine
programmed cell death ligand 2
Programmed Cell Death 1 Ligand 2 Protein
medicine.disease
oral squamous cell carcinoma
Gene Expression Regulation
Neoplastic
stomatognathic diseases
STAT1 Transcription Factor
030104 developmental biology
medicine.anatomical_structure
Oncology
Drug Resistance
Neoplasm
Tissue Array Analysis
Cell culture
030220 oncology & carcinogenesis
Cancer cell
Carcinoma
Squamous Cell
Cancer research
biology.protein
Original Article
Female
Mouth Neoplasms
medicine.drug
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.14336
Popis: Programmed cell death ligands (PD‐Ls) are expressed in tumor cells where they bind to programmed cell death‐1, an immunocyte co–receptor, resulting in tumor cell evasion from the immune system. Chemotherapeutic drugs have been recently reported to induce the expression of PD‐L, such as PD‐L1, in some cancer cells. However, little is known regarding PD‐L2 expression and its role in oral squamous cell carcinoma (OSCC). In this study, we examined the effect of cisplatin on the expression and regulation of PD‐L2 in OSCC cell lines and analyzed malignant behavior in PD‐L2‐expressing cells using colony, transwell and transformation assays. In addition, we examined PD‐L2 expression in the tumor tissues of OSCC patients using cytology and tissue microarray methods. In OSCC cell lines, cisplatin treatment upregulated PD‐L2 expression, along with that of the drug efflux transporter ABCG2, via signal transducers and activator of transcription (STAT) 1/3 activation. Moreover, PD‐L2‐positive or PD‐L2‐overexpressing cells demonstrated upregulation in both invasion and transformation ability but not in proliferation compared with PD‐L2‐negative or PD‐L2‐silencing cells. PD‐L2 expression was also observed in OSCC cells of cytology samples and tissue from OSCC patients. The intensity of PD‐L2 expression was correlated with more malignant morphological features in the histological appearance and an invasive pattern. Our findings indicate that cisplatin‐upregulated PD‐L2 expression in OSCC via STAT1/3 activation and the expression of PD‐L2 are likely to be associated with malignancy in OSCC. The PD‐L2 expression in cisplatin‐resistant OSCC cells may be a critical factor in prognosis of advanced OSCC patients.
Our findings indicate that cisplatin‐upregulated PD‐L2 expression in oral squamous cell carcinoma (OSCC) cells via STAT1/3 activation and the expression of PD‐L2 are likely to be associated with malignancy in OSCC. The PD‐L2 expression in cisplatin‐resistant OSCC cells may be a critical factor in the prognosis of advanced OSCC patients.
Databáze: OpenAIRE
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