Related Experiment Video
Updated: Apr 7, 2026
Glycomics-Guided Glycoproteomics Facilitates Comprehensive Profiling of the Glycoproteome in Complex Tumor Microenvironments
Published on: February 7, 2025
Comprehensive Glycomics of a Multistep Human Brain Tumor Model Reveals Specific Glycosylation Patterns Related to
Jun-ichi Furukawa1, Masumi Tsuda2, Kazue Okada1
1Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Abstract:
Cancer cells frequently express glycans at different levels and/or with fundamentally different structures from those expressed by normal cells, and therefore elucidation and manipulation of these glycosylations may provide a beneficial approach to cancer therapy. However, the relationship between altered glycosylation and causal genetic alteration(s) is only partially understood. Here, we employed a unique approach that applies comprehensive glycomic analysis to a previously described multistep tumorigenesis model. Normal human astrocytes were transformed via the serial introduction of hTERT, SV40ER, H-RasV12, and myrAKT, thereby mimicking human brain tumor grades I-IV. More than 160 glycans derived from three major classes of cell surface glycoconjugates (N- and O-glycans on glycoproteins, and glycosphingolipids) were quantitatively explored, and specific glycosylation patterns related to malignancy were systematically identified. The sequential introduction of hTERT, SV40ER, H-RasV12, and myrAKT led to (i) temporal expression of pauci-mannose/mono-antennary type N-glycans and GD3 (hTERT); (ii) switching from ganglio- to globo-series glycosphingolipids and the appearance of Neu5Gc (hTERT and SV40ER); (iii) temporal expression of bisecting GlcNAc residues, α2,6-sialylation, and stage-specific embryonic antigen-4, accompanied by suppression of core 2 O-glycan biosynthesis (hTERT, SV40ER and Ras); and (iv) increased expression of (neo)lacto-series glycosphingolipids and fucosylated N-glycans (hTERT, SV40ER, Ras and AKT). These sequential and transient glycomic alterations may be useful for tumor grade diagnosis and tumor prognosis, and also for the prediction of treatment response.
Insights
Cancer cells show distinct glycan patterns. This study maps these changes during brain tumor development, offering potential for diagnosis and treatment prediction.
Area of Science:
- Biochemistry
- Glycobiology
- Cancer Research
Background:
- Cancer cells exhibit altered glycosylation compared to normal cells, impacting therapeutic strategies.
- The link between genetic alterations and aberrant glycosylation in cancer is not fully understood.
Purpose of the Study:
- To comprehensively analyze glycomic changes during multistep brain tumorigenesis.
- To identify specific glycosylation patterns associated with different tumor grades and stages.
Main Methods:
- Utilized a multistep human astrocyte transformation model (hTERT, SV40ER, H-RasV12, myrAKT) mimicking brain tumor progression.
- Performed quantitative glycomic analysis of over 160 glycans from N-glycans, O-glycans, and glycosphingolipids.
Main Results:
- Identified sequential glycomic alterations correlating with tumor grade progression.
- Observed temporal expression of specific N-glycans (pauci-mannose), glycosphingolipids (GD3, globo-series, lacto-series), and modifications (Neu5Gc, bisecting GlcNAc, fucosylation).
- Noted suppression of core 2 O-glycan biosynthesis and appearance of stage-specific embryonic antigen-4.
Conclusions:
- Sequential and transient glycomic alterations are characteristic of brain tumor development.
- These identified glycomic signatures may serve as biomarkers for tumor diagnosis, prognosis, and treatment response prediction.
