Glycoproteomics of paclitaxel resistance in human epithelial ovarian cancer cell lines: Towards the identification of putative biomarkers

Michela Di Michele, Simone Marcone, Lucia Cicchillitti, Anna Della Corte, Cristiano Ferlini, Giovanni Scambia, Maria Benedetta Donati, Domenico Rotilio

Research output: Contribution to journalArticle

Abstract

Glycosylation, one of the most common post translational modifications (PTMs) of proteins, is often associated with carcinogenesis and tumor malignancy. Ovarian cancer is the sixth cause of cancer-related death in Western countries. Currently, it is treated by debulking surgery followed by chemotherapy based on paclitaxel, alone or in combination with other drugs. However, chemoresistance represents a major obstacle to positive clinical outcome. We used two approaches, Multiplexed Proteomics (MP) technology and Multilectin Affinity Chromatography (MAC) to characterize the glycoproteome of the human ovarian cancer cell line A2780 and its paclitaxel resistant counterpart A2780TC1. Furthermore proteins were separated by traditional 2DE or DIGE and identified by MS (MALDI TOF or LC MS/MS). Seventy glycoproteins were successfully identified in ovarian cancer cells and 10 were found to be differentially expressed between sensitive and resistant cell lines. We focused on four glycoproteins (tumor rejection antigen (gp96) 1, triose phosphate isomerase, palmitoyl-protein thioesterase 1 precursor and ER-associated DNAJ) which were remarkably upregulated in A2780TC1 compared to A2780 cell line and which may represent biomarkers for paclitaxel resistance in ovarian cancer.

Original languageEnglish
Pages (from-to)879-898
Number of pages20
JournalJournal of Proteomics
Volume73
Issue number5
DOIs
Publication statusPublished - Mar 10 2010

Keywords

  • Biomarker
  • DIGE
  • Glycoproteome
  • Ovarian cancer
  • Paclitaxel resistance

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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