Quantitative structural analysis of glycans expressed within tumors derived from pancreatic cancer patient-derived xenograft mouse models

• Published in: Biochemical and biophysical research communications Vol. 534; pp. 310 - 316
• Main Authors: Hasehira, Kayo, Furuta, Tomoaki, Shimomura, Osamu, Asada, Masahiro, Oda, Tatsuya, Tateno, Hiroaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2021
• Subjects: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Carcinoma, Pancreatic Ductal - chemistry; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Cell Differentiation; Cell Line, Tumor; Female; Fucose; Glycan; Glycomics; H-type3; Heterografts; Humans; Mice; Mice, SCID; Molecular Structure; Neoplasm Transplantation; Pancreatic cancer; Pancreatic Neoplasms - chemistry; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Polysaccharides - chemistry; Polysaccharides - metabolism; rBC2LCN; MPC; PDX; hPSC; LDC; LAPC; Glycan; LC50; PA; H-type3; PDAC; Pancreatic cancer; rBC2LCN; Fucose
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.11.087

Pancreatic ductal adenocarcinoma (PDAC) is an intractable malignancy for which novel therapeutic targets are in high demand. To uncover glycans expressed within PDAC, we previously performed glycome profiling of PDAC cell lines using lectin microarray and found that the lectin rBC2LCN with specificity to a Fucα1-2Galβ1-3 motif exhibited strong binding to a PDAC cell line (Capan-1) and to all tumor tissues derived from 69 pancreatic cancer patients. Nevertheless, no information was available as to whether glycans containing the Fucα1-2Galβ1-3 motif are expressed within PDAC. Here we used HPLC combined with MALDI-TOFMS to perform a structural and quantitative glycome analysis targeting both N- and O-glycans derived from two types of patient-derived PDAC xenograft mouse models, PC3 (well-differentiated) and PC42 (poorly-differentiated). A higher percentage of highly branched and sialylated complex-type N-glycans was detected in PC42 relative to PC3. The percentage of core 1 O-glycans was higher in PC42 relative to PC3, whereas that of core 3 O-glycans was higher in PC3. Cancer-related glycan epitopes such as Lewis A and Lewis Y were detected in core 3 O-glycans of both PC3 and PC42. H-type3 containing the Fucα1-2Galβ1-3 motif was detected in Core 2 O-glycans in both models, explaining the molecular mechanism of the binding of rBC2LCN to PDAC.
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•Glycan structures of tumors from two PDAC PDX models were analyzed.•Distinct protein glycosylation was observed between the two PDAC PDX models.•Core2 H-type3 was detected in tumors of both PDAC PDX models.