Role of Wisteria floribunda agglutinin binding glycans in carcinogenesis and metastasis of cholangiocarcinoma.

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.

Targeting alpha2,3-sialylated glycan in glioma stem-like cells by Maackia amurensis lectin-II: A promising strategy for glioma treatment.

Glioma stem/initiating cells have been considered a major cause of tumor recurrence and therapeutic resistance. In this study, we have established a new glioma stem-like cell (GSC), named U373-GSC, from the U373 glioma cell line. The cells exhibited stemness properties, e.g., expression of stem cell markers, self-renewal activity, multi-lineage differentiating abilities, and drug resistance. Using U373-GSC and GSC-03A-a GSC clone previously established from patient tissue, we have identified a novel GSC-associated sialic acid-modified glycan commonly expressed in both cell lines. Lectin fluorescence staining showed that Maackia amurensis lectin II (MAL-II)-binding alpha2,3-sialylated glycan (MAL-SG) was highly expressed in GSCs, and drastically decreased during FBS induced differentiation to glioma cells or little in the parental cells. Treatment of GSCs by MAL-II, compared with other lectins, showed that MAL-II significantly suppresses cell viability and sphere formation via induction of cell cycle arrest and apoptosis of the GSCs. Similar effects were observed when the cells were treated with a sialyltransferase inhibitor or sialidase. Taken together, we demonstrate for the first time that MAL-SGs/alpha-2,3 sialylations are upregulated and control survival/maintenances of GSCs, and their functional inhibitions lead to apoptosis of GSCs. MAL-SG could be a potential marker and therapeutic target of GSCs; its inhibitors, such as MAL-II, may be useful for glioma treatment in the future.

Carbohydrate Antigen 50: Values for Diagnosis and Prognostic Prediction of Intrahepatic Cholangiocarcinoma.

Background and objectives: Cancer-associated carbohydrate antigen 50 (CA50) is a marker for detection of gastrointestinal cancers, especially of pancreatic and colon cancer. In this study, the power of CA50 as a diagnostic and prognostic marker was evaluated in intrahepatic cholangiocarcinoma (iCCA). Materials and Methods: Serum CA50 levels of iCCA patients and non-cholangiocarcinoma controls (non-CCA, including healthy persons and patients with benign biliary diseases and other gastrointestinal cancers) were measured using MAGLUMI®800 CLIA analyzer. Diagnostic and prognostic values of serum CA50 levels were evaluated. Results: CA50 levels in the sera of iCCA patients were significantly higher than those of non-CCA controls (p < 0.001, Mann-Whitney U test). Using cut-off value of 25 U/mL, CA50 provided 65.9% sensitivity, 87.3% specificity, and 80.1% accuracy for diagnosis of iCCA. Serum CA50 levels were increased and associated with the severity of bile duct pathology. In addition, a higher level of CA50 was associated with poor clinical outcome and shorter survival in iCCA patients. Multivariate survival analysis by Cox regression model revealed the potential of CA50 as an independent poor prognostic indicator for iCCA, regardless of the age, sex, histological types, or tumor stages. Conclusions: CA50 can be a diagnostic and poor prognostic marker candidate for iCCA.