Abstract
Aberrant glycosylation is an important factor in facilitating tumor progression and therapeutic resistance. In this study, using Wisteria floribunda agglutinin (WFA), we examined the expression of WFA-binding glycans (WFAG) in cholangiocarcinoma (CCA). The results showed that WFAG was highly detected in precancerous and cancerous lesions of human CCA tissues, although it was rarely detected in normal bile ducts. The positive signal of WFAG in the cancerous lesion accounted for 96.2% (50/52) of the cases. Overexpression of WFAG was significantly associated with lymph node and distant metastasis (P < 0.05). The study using the CCA hamster model showed that WFAG is elevated in preneoplastic and neoplastic bile ducts as early as 1 month after being infected with liver fluke and exposed to N-nitrosodimethylamine. Functional analysis was performed to reveal the role of WFAG in CCA. The CCA cell lines KKU-213A and KKU-213B were treated with WFA, followed by migration assay. Our data suggested that WFAG facilitates the migration of CCA cells via the activation of the Akt and ERK signaling pathways. In conclusion, we have demonstrated the association of WFAG with carcinogenesis and metastasis of CCA, suggesting its potential as a target for the treatment of the disease.
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This project was funded by Kasetsart University through the Graduate School Fellowship Program and Faculty of Public Health, Kasetsart University, Thailand, to W.P. and S.C. and by the Fundamental Fund of Khon Kaen University (FF65) to A.S. We thank Prof. Yukifumi Nawa for English editing via the KKU publication clinic.
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Fundamental Fund of Khon Kaen University (FF65). Kasetsart University through the Graduate School Fellowship Program
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W.P., S.P., O.P., P.M., K.T., and M.D. performed experiments and analyzed data; W.P., S.P, and P.M. prepared Figs. 1–2; W.P., O.P., P.S., and S.U. prepared Figs. 3–4; T.S., A.K., P.M., and S.L. supervised experiment handling and data analysis; S.C. and A.S. designed the study and funding acquisition; and W.P., S.P., S.C., and A.S. wrote and edited manuscript.
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Phuyathip, W., Putthisen, S., Panawan, O. et al. Role of Wisteria floribunda agglutinin binding glycans in carcinogenesis and metastasis of cholangiocarcinoma. Histochem Cell Biol 161, 423–434 (2024). https://doi.org/10.1007/s00418-024-02270-4
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DOI: https://doi.org/10.1007/s00418-024-02270-4