Precise mapping of increased sialylation pattern and the expression of acute phase proteins accompanying murine tumor progression in BALB/c mouse by integrated sera proteomics and glycomics

Shu Yu Lin, Yi Yun Chen, Yao Yun Fan, Chia Wei Lin, Shui Tsung Chen, Andrew H.J. Wang, Kay Hooi Khoo

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Inbred BALB/c mouse implanted with murine tumors serves as an attractive model system for the studies of cancer biology in immuno-competent individuals. It is anticipated that tumor progression would induce notable pathophysiological consequences, some of which manifested as alteration in serum proteomic and glycomic profiles. Similar to sera derived from human cancer patients and immunocompromised mice bearing human tumors, we show in this work that BALB/c mice of the same genetic background but bearing two distinct tumor origins both exhibited elevated expression levels of acute phase proteins including haptoglobin and serum amyloid P protein, in response to tumor progression. Such common traits are generally not informative nor qualifying as biomarkers. Additional mass spectrometry (MS)-based glycomic mapping nevertheless detected distinctive changes of sialylation pattern on the complex type N-glycans. MALDI MS/MS sequencing afforded a facile but definitive identification ofan increase in internal Neu5Gcα2-6 sialylation on the GlcNAc of the Neu5Gc2-3Gal1-3GlcNAc terminal sequence as a common feature whereas a substitution of Neu5Gc by Neu5Ac was found to be induced by colonic but not breast tumor. A more pronounced change was similarly detected on N-glycans derived from ascitic fluids representing late tumor progression stages. We next demonstrated that such distinct change in glycotope expression can be localized to a particular protein carrier by LC-MS/MS analysis of glycopeptides. Serotransferrin was identified as one such abundant serum glycoprotein, which changed significantly not in protein expression level but in terminal glycosylation pattern.

Original languageEnglish
Pages (from-to)3293-3303
Number of pages11
JournalJournal of Proteome Research
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

Keywords

  • Acute phase proteins
  • Ascitic fluids
  • Glycomics
  • Mass spectrometry
  • Serum proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'Precise mapping of increased sialylation pattern and the expression of acute phase proteins accompanying murine tumor progression in BALB/c mouse by integrated sera proteomics and glycomics'. Together they form a unique fingerprint.

Cite this