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

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.福岡歯科大学2019年

Correlative Expression of Cyclooxygenase-1 (Cox-1) and Human Epidermal Growth Factor Receptor Type-2 (Her-2) in Endometrial Cancer

Objectives: Cyclooxygenase-2 (Cox-2) is known to be associated with tumorigenesisin many cancers including endometrial cancer, while there is substantial evidence forthe tumorigenicity of cyclooxygenase-1 (Cox-1). However, little is known about theinvolvement of Cox-1 in the development of endometrial cancer. The aim of this studywas to determine whether cyclooxygenase-1 or -2 (Cox-1, Cox-2) is tumorigenetic, aswell as whether these two cyclooxygenase isoforms correlate with theclinicopathological characteristics or with another two biomarkers, human epidermalgrowth factor receptor type-2 (Her-2) and vascular endothelial growth factor (VEGF),of endometrial cancer.Methods: At first, Cox-1 and Cox-2 levels in eight endometrial cancer cell lines weredetermined by means of real-time PCR. At second, the levels of four biomarkers (Cox-1,Cox-2, Her-2, and VEGF) in 70 endometrial cancer samples were determined by meansof real-time PCR. Pairs of these biomarkers were subjected to correlation as eachbiomarker and clinical status or survival.Results: In the eight cell lines, the expression of Cox-1 and Cox-2 showed majorvariations in their mRNA levels. Analysis of the patient samples showed that the mRNAexpression of Cox-1 was elevated significantly in the G1 (P=0.021) and G2 (P=0.036)groups, as was the mRNA expression of Her-2 in the two groups (P=0.036 and P=0.0029,respectively). The mRNA expression of Cox-1 and Her-2 were correlated (CI=0.671).None of the three biomarkers, Cox-1, Cox-2, and Her-2, was correlated with clinicalstatus such as FIGO classification, myometrial invasion, or clinical outcome.Conclusion: Cox-1, together with Her-2, may be involved in the early stage ofendometrial cancer development