Nectin-2 is overexpressed in cancer cells and is associated with poor prognosis in patients with various types of cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study aimed to investigate the expression pattern of Nectin-2, its clinical significance and its roles in the malignant phenotypes of ESCC. Expression levels of Nectin-2 mRNA and protein were respectively detected by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry, based on 106 newly diagnosed ESCC patients. The associations between Nectin-2 expression and clinicopathological characteristics of ESCC patients were statistically analyzed. The effects of Nectin-2 in migration and invasion were then determined by wound healing and Transwell assays performed using ESCC cell lines (ECA109 and KYSE510) transfected with small interfering (si) RNA against Nectin-2. It was found that Nectin-2 expression was significantly elevated at the mRNA and protein levels in ESCC tissues, compared with the normal esophageal mucosa (P<0.001). Nectin-2-positive immunoreactivity was mainly localized in the cytoplasm of cancer cells in ESCC tissues. In addition, the expression levels of Nectin-2 protein in ESCC tissues with advanced tumor stage (P=0.006) and poor differentiation (P=0.02) were increased compared with patients with early tumor stage and well to moderate differentiation. Additionally, knockdown of Nectin-2 in the 2 ESCC cell lines could effectively suppress the cell migration and invasion abilities (P<0.05). In conclusion, these findings revealed that Nectin-2 is generally overexpressed in ESCC and associated with aggressive cancer progression. The present data also indicated that the silencing of Nectin-2 with siRNA in ESCC cells may inhibit cell malignant biological properties, indicating its potential as a potential marker or a therapeutic target for ESCC.
Keywords: Nectin-2; esophageal squamous cell carcinoma; invasion; migration; progression.