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.
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 immuno-compromised 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 of an increase in internal Neu5Gcalpha2-6 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.
NRPGM Core Facilities for Proteomic Research, and Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei, Taiwan.
Shu-Yu
SY
Lin
Yi-Yun
YY
Chen
Yao-Yun
YY
Fan
Chia-Wei
CW
Lin
Shui-Tsung
ST
Chen
Andrew H-J
AH
Wang
Kay-Hooi
KH
Khoo
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D002853:Chromatography, Liquid; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D054794:Glycomics; D006020:Glycopeptides / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D040901:Proteomics; D012794:Sialic Acids / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
D000209:Acute-Phase Proteins; D006020:Glycopeptides; D006023:Glycoproteins; D012794:Sialic Acids