Quantitative structural analysis of glycans expressed within tumors derived from pancreatic cancer patient-derived xenograft mouse models
Autor: | Masahiro Asada, Osamu Shimomura, Kayo Hasehira, Tatsuya Oda, Hiroaki Tateno, Tomoaki Furuta |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Glycan endocrine system diseases Microarray Biophysics Mice SCID Biochemistry Fucose Epitope Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Polysaccharides Cell Line Tumor Pancreatic cancer Carbohydrate Conformation medicine Animals Humans Glycomics Molecular Biology Molecular Structure biology Chemistry Lectin Cell Differentiation Cell Biology medicine.disease Glycome digestive system diseases Pancreatic Neoplasms carbohydrates (lipids) 030104 developmental biology Carbohydrate Sequence Cell culture 030220 oncology & carcinogenesis biology.protein Cancer research Heterografts Female Neoplasm Transplantation Carcinoma Pancreatic Ductal |
Zdroj: | Biochemical and Biophysical Research Communications. 534:310-316 |
ISSN: | 0006-291X |
Popis: | 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. |
Databáze: | OpenAIRE |
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