Identification of LCA-binding Glycans as a Novel Biomarker for Esophageal Cancer Metastasis using a Lectin Array-based Strategy

Esophageal cancer (EC) is a unique and heterogeneous disease diagnosed mostly at advanced stages. Altered glycans presented on cell surfaces are involved in the occurrence and development of malignancy. However, the effects of glycans on EC progression are largely unexplored. Here, a lectin array was utilized to detect the glycan profiling of the normal esophageal mucosal epithelial cell line and two EC cell lines. The binding of Lens culinaris lectin (LCA) to EC cells was found to be stronger than that of the normal cells. Lectin immunohistochemical staining revealed that LCA-binding glycans were markedly elevated in EC tissues compared to adjacent non-cancerous tissues. LCA staining was significantly associated with lymph node metastasis, depth of invasion, TNM stage and poor overall survival of EC patients. Added LCA to block LCA recognized glycans could inhibit the migration and invasion of EC cells. Further analysis revealed that blocking the biosynthesis of LCA-binding glycans by tunicamycin attenuated cellular migratory and invasive abilities. Additionally, a membrane glycoprotein CD147 was recognized as a binder of LCA. There was a positive correlation between LCA-binding glycans and CD147 expression in clinical samples. Interestingly, CD147 inhibition also reduced cell migration and invasion. These findings indicated that LCA-binding glycans may function as a novel indicator to predict metastasis for patients with EC.