Glycoproteomics of paclitaxel resistance in human epithelial ovarian cancer cell lines: towards the identification of putative biomarkers.
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.
Di Michele
Michela
M
Research Laboratories, John Paul II Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy. michela.dimichele@moli-sani.org
Marcone
Simone
S
Cicchillitti
Lucia
L
Della Corte
Anna
A
Ferlini
Cristiano
C
Scambia
Giovanni
G
Donati
Maria Benedetta
MB
Rotilio
Domenico
D
D015415:Biomarkers; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000032:analysis* / Q000235:genetics; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D013869:Thiolester Hydrolases / Q000235:genetics; D014305:Triose-Phosphate Isomerase / Q000235:genetics; D015854:Up-Regulation
D015415:Biomarkers; D006023:Glycoproteins; D050956:HSP40 Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D014305:Triose-Phosphate Isomerase; D017239:Paclitaxel