High-mannose glycans are elevated during breast cancer progression

Maria Lorna A De Leoz, Lawrence J T Young, Hyun Joo An, Scott R. Kronewitter, Jaehan Kim, Suzanne Miyamoto, Alexander D Borowsky, Helen K Chew, Carlito B Lebrilla

Research output: Contribution to journalArticlepeer-review

194 Scopus citations


Alteration in glycosylation has been observed in cancer. However, monitoring glycosylation changes during breast cancer progression is difficult in humans. In this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle T antigen, to observe early changes in glycosylation. We have previously used the said mouse model to look at O-linked glycosylation changes with breast cancer. In this glycan biomarker discovery study, we examined N-linked glycan variations during breast cancer progression of the mouse model but this time doubling the number of mice and blood draw points. N-glycans from total mouse serum glycoproteins were profiled using matrix-assisted laser desorption/ionization Fourier transform-ion cyclotron resonance mass spectrometry at the onset, progression, and removal of mammary tumors. We observed four N-linked glycans, m/z 1339.480 (Hex3HexNAc), 1485.530 (Hex3HexNAc4Fuc), 1809.639 (Hex5HexNAc4Fuc), and 1905.630 (Man9), change in intensity in the cancer group but not in the control group. In a separate study, N-glycans from total human serum glycoproteins of breast cancer patients and controls were also profiled. Analysis of human sera using an internal standard showed the alteration of the low-abundant high-mannose glycans, m/z 1419.475, 1581.528, 1743.581, 1905.634 (Man6-9), in breast cancer patients. A key observation was the elevation of a high-mannose type glycan containing nine mannoses, Man9, m/z 1905.630 in both mouse and human sera in the presence of breast cancer, suggesting an incompletion of the glycosylation process that normally trims back Man 9 to produce complex and hybrid type oligosaccharides.

Original languageEnglish (US)
JournalMolecular and Cellular Proteomics
Issue number1
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry
  • Medicine(all)


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