Glycoproteomic analysis of glioblastoma stem cell differentiation

Jintang He, Yashu Liu, Thant S. Zhu, Xiaolei Xie, Mark A. Costello, Caroline E. Talsma, Callie G. Flack, Jessica G. Crowley, Francesco DiMeco, Angelo L. Vescovi, Xing Fan, David M. Lubman

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Cancer stem cells are responsible for tumor formation through self-renewal and differentiation into multiple cell types and thus represent a new therapeutic target for tumors. Glycoproteins play a critical role in determining the fates of stem cells such as self-renewal, proliferation, and differentiation. Here we applied a multilectin affinity chromatography and quantitative glycoproteomics approach to analyze alterations of glycoproteins relevant to the differentiation of a glioblastoma-derived stem cell line HSRGBM1. Three lectins including concanavalin A (Con A), wheat germ agglutinin (WGA), and peanut agglutinin (PNA) were used to capture glycoproteins, followed by LC-MS/MS analysis. A total of 73 and 79 high-confidence (FDR <0.01) glycoproteins were identified from the undifferentiated and differentiated cells, respectively. Label-free quantitation resulted in the discovery of 18 differentially expressed glycoproteins, wherein 9 proteins are localized in the lysosome. All of these lysosomal glycoproteins were up-regulated after differentiation, where their principal function was hydrolysis of glycosyl residues. Protein-protein interaction and functional analyses revealed the active involvement of lysosomes during the process of glioblastoma stem cell differentiation. This work provides glycoprotein markers to characterize differentiation status of glioblastoma stem cells that may be useful in stem-cell therapy of glioblastoma.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalJournal of Proteome Research
Volume10
Issue number1
DOIs
StatePublished - Jan 7 2011

Keywords

  • Cell differentiation
  • Glioblastoma
  • Glycoprotein
  • LC-MS/MS
  • Lectin affinity chromatography
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry
  • General Chemistry

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