The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG-1 metastasis markers and leads to the identification of DJ-1 as a potential serum biomarker.
Uveal malignant melanoma (UM) is the most frequent primary intraocular tumour in adult humans. Because the survival rate of patients with UM has changed little in the past few decades, a better understanding of the molecular events governing UM development and the identification of markers indicating the potential for metastasis at the time of diagnosis are necessary to design improved and more specific treatments. In this study, we investigated UM tumour development by comparing two recently established UM cultures with different invasion potential by two-dimensional gel electrophoresis. Protein features expressed differentially were identified by mass spectrometric analysis. Potential markers were assayed in both cultures and in long-term established UM cell lines (UW-1, OCM-1, SP6.5 and 92.1) by Western blotting and their role in invasion analysed using Matrigel membranes. Comparative analysis revealed that UM cultures with low- and high-grade invasion potential differ in their cellular metabolism and, more interestingly, in several cancer-associated proteins, including those implicated in cell adhesion and migration, proliferation and various oncogenes. Our data indicate a correlation between MUC18 and HMG-1 expression and the invasiveness of UM cells. We also demonstrate the expression and secretion of DJ-1 oncoprotein by UM cells. We suggest a possible role for MUC18 and HMG-1 proteins in UM cell invasion. The secretion of DJ-1 by UM cells, and the ability to detect this protein in UM patients' sera implicate it as a potential noninvasive biomarker for this malignancy.
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, UK. maruxapardo@hotmail.com
María
M
Pardo
Angel
A
García
Benjamin
B
Thomas
Antonio
A
Piñeiro
Alexandre
A
Akoulitchev
Raymond A
RA
Dwek
Nicole
N
Zitzmann
D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D051929:CD146 Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D024243:HMGB1 Protein / Q000032:analysis*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D013058:Mass Spectrometry; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D015513:Oncogene Proteins / Q000032:analysis*; D010641:Phenotype; D000071617:Protein Deglycase DJ-1; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D024243:HMGB1 Protein; D047908:Intracellular Signaling Peptides and Proteins; C497902:MCAM protein, human; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1