Clinical impacts of Artocarpus lakoocha agglutinin-binding glycans for prognosis and treatment of cholangiocarcinoma

Abstract

Abstract Artocarpus lakoocha agglutinin (ALA), which specifically targets the Gal/GalNAc components of complex glycans, was isolated from the seeds of Artocarpus lakoocha. This study is the first to explore the role of ALA in identifying aberrant glycans, designated ALA-binding glycans (ALAG), and its implications in cholangiocarcinoma (CCA). ALA-histochemistry was used to evaluate ALAG expression in liver fluke-induced CCA tissues from hamsters (n = 60). Elevated ALAG expression was observed in hyperplastic ducts and significantly increased in CCA tissues, while normal biliary epithelium and hepatocytes showed no expression. Similar results were found in patient CCA tissues (n = 68), where higher ALAG levels correlated with shorter survival rates, indicating the involvement of ALAG in CCA development and progression. Furthermore, ALA treatment inhibited cell viability in CCA cell lines, as demonstrated by MTT and colony formation assays, and Ki-67 expression. ALA treatment also decreased cell migration and invasion, as shown by Transwell assays. Gelatin zymography suggested that these effects might be associated with reduced MMP-9 activity. Overall, these findings may position ALAG as a potential marker for poor prognosis in CCA, while ALA may serve as a novel lectin for both detection and therapeutic applications in CCA.

Keywords

• Artocarpus lakoocha agglutinin
• Cholangiocarcinoma
• Aberrant glycosylation
• T and Tn antigens
• Anti-metastasis
• Anti-proliferation