2022 年 56 巻 1 号 p. 51-61
Tumor progression and metastasis occur by a variety of mechanisms, including epithelial-mesenchymal transition (EMT) and PD-1/PD-L1 signaling. In addition, hepatocyte growth factor (HGF) induces EMT in cancer, so the HGF/c-Met pathway is being elucidated. Epidermal growth factor (EGF) is overexpressed in cancer cells and is considered to be a poor prognosis factor for cancer. Furthermore, it has been reported that PD-L1 expression is associated with HGF/c-Met and EGF/EGFR. Therefore, in this study, we investigated the relationship between HGF/c-Met signal and PD-L1 expression using oral squamous cell carcinoma (OSCC) cell lines. PD-L1 expression was enhanced by HGF and EGF treatments alone using Western Blotting. However, c-Met inhibitory treatment did not suppress the PD-L1 expression. In addition, PD-L1 was suppressed by EGFR inhibitor treatment. Therefore, it was investigated whether treatment with SU11274, which is a c-Met inhibitor, acts on the activity of EGF receptor, p-EGFR in HSC3 and SAS. As a result, high expression of p-EGFR was observed.
Furthermore, when SU11274 and AG1478 were used together, PD-L1 was significantly reduced in both HSC3 and SAS. Immunostaining showed that SU11274 alone did not change the expression of PD-L1 found mainly in the cell membrane, but the AG1478 treatment tended to significantly reduce the expression of PD-L1. Furthermore, the expression of PD-L1 was significantly reduced when both were added. These results suggested that the expression of PD-L1 in the OSCC cell line is regulated by the mutual balance between the HGF/c-Met and the EGF/EGFR signal. From the regulating the expression of PD-L1 point of view, it is effective to use the potent EGFR tyrosine kinase inhibitor AG1478 in combination with c-Met inhibition. (J Osaka Dent Univ 2022; 56: 51-61)
