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

Abstract

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 twodimensional 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 lowand 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. ' 2006 Wiley-Liss, Inc.Key words: uveal melanoma; invasion; proteomics; MUC-18; DJ-1 Uveal malignant melanoma (UM) is the most frequent intraocular tumour in adult humans.1 Unlike cutaneous melanoma, uveal melanoma disseminates mainly through the blood stream and preferentially establishes metastases in the liver. Metastatic liver disease is the leading cause of death in uveal melanoma and can develop after a long disease-free interval, which suggests the presence of occult micrometastatic disease at the time the primary eye tumour is diagnosed and treated.2 Unfortunately, advances in eye cancer treatment have not paralleled those made in the management of other types of cancer, and the survival rate of patients with uveal melanoma has changed little in the past few decades.3 A better understanding of the molecular events governing uveal melanoma 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. Various clinical and molecular prognostic factors have been suggested in uveal melanoma, but none has proved to be sufficiently useful or viable for routine clinical use. 4,5 Currently, there are many challenging technologies and approaches to identify tumour markers for prognostic and therapeutic purposes.6 Transcriptional studies alone are not sufficient, with several investigators reporting a poor correlation between mRNA and p...

DJ-1 Could Predict Worse Prognosis in Esophageal Squamous Cell Carcinoma

“…A potential use of serum DJ-1 as a tumor marker has been suggested in some cancers (12,37). Together with the results in the present study, serum DJ-1 is an attractive target to be studied for its potential use as a noninvasive biomarker for ESCC progression and prognosis.…”

Treatment with diphenyl–pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death

“…Two other genes, which have been linked to PD, are DJ-1 and ATP13A2. We did not determine the status of expression of DJ-1 in tissues ranging from nevi > advanced melanoma, but a histopathological study has shown that, in cutaneous melanoma, cytoplasmic expression of DJ-1 is decreased (21), whereas in the serum of patients with metastatic uveal melanoma it is elevated (22,23). To date, it is not known whether ATP13A2 plays a role in melanoma, but in light of its putative interplay with α-synuclein (24), it is noteworthy that the ATP13A2-specific dataset from our previously conducted whole-genome expression profiling study indicates that, as in the case of SNCA, the ATP13A2 gene is upregulated with progression from nevi > melanoma.…”

Proteomics Identification of ITGB3 as a Key Regulator in Reactive Oxygen Species-induced Migration and Invasion of Colorectal Cancer Cells

“…DJ-1 was originally identified as a putative oncogene (58) and has been shown to be a negative regulator of the tumor suppressor PTEN (59). Pardo et al discovered DJ-1 as a potential serum biomarker for uveal malignant melanoma (60). SOD-1 has been shown to exert variable roles in cancer cells: overexpression of SOD-1 inhibited breast cancer cell growth and invasion (61) …”