Proteomic analysis of uveal melanoma reveals novel potential markers involved in tumor progression.

PURPOSE Patient survival in uveal melanoma may benefit from earlier recognition of potential metastases to the liver, but as yet, proper markers indicating metastases are not available. Identification of metastasis markers would therefore be of great value. The proteins that are expressed in two cell lines originating from two liver metastases were compared with the proteins expressed in a cell line obtained from the primary uveal melanoma of the same patient, to identify proteins that play a role in tumor progression as well as proteins that are expressed specifically in metastases. METHODS Protein analysis was performed by using two-dimensional gel electrophoresis. A subset of proteins was subsequently identified with mass spectrometry. RESULTS A set of 24 proteins was differentially expressed in both of the two metastatic cell lines compared with the cell line derived from the primary tumor. These proteins were subdivided into groups according to cellular function, with important roles in tumor development. CONCLUSIONS Tumor progression and development of metastases is a multicomplex system. Comparing protein expression in two cell lines derived from metastases with a cell line derived from a primary uveal melanoma from the same patient identified proteins involved in tumor progression, and proteins specifically expressed in the metastases, which have the potential of becoming clinically useful biomarkers.

[1]  M. Ponec,et al.  Proteomic profiling identifies an UV-induced activation of cofilin-1 and destrin in human epidermis. , 2005, The Journal of investigative dermatology.

[2]  Hans E. Grossniklaus,et al.  Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. Onken MD, Worley LA, Ehlers JP, Harbour JW Canc Res 2004;64:7205–7209 , 2005 .

[3]  G. Rabinovich,et al.  Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase , 2004, Molecular and Cellular Biochemistry.

[4]  Justis P. Ehlers,et al.  Gene Expression Profiling in Uveal Melanoma Reveals Two Molecular Classes and Predicts Metastatic Death , 2004, Cancer Research.

[5]  A. Raz,et al.  Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis , 2004, Cancer and Metastasis Reviews.

[6]  S. Pavey,et al.  Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development. , 2004, International journal of cancer.

[7]  J. Keunen,et al.  Proteomics in uveal melanoma , 2003, Melanoma research.

[8]  R. Frants,et al.  Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development , 2003, British Journal of Cancer.

[9]  S. Libutti,et al.  Angiogenesis inhibitors target the endothelial cell cytoskeleton through altered regulation of heat shock protein 27 and cofilin. , 2003, Cancer research.

[10]  D. Ferrigno,et al.  Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC). , 2003, Lung cancer.

[11]  J. Keunen,et al.  Heat shock protein expression in the eye and in uveal melanoma. , 2003, Investigative ophthalmology & visual science.

[12]  K. Jöckel,et al.  Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. , 2003, Cancer research.

[13]  Giuseppe Musumarra,et al.  A Bioinformatic Approach to the Identification of Candidate Genes for the Development of New Cancer Diagnostics , 2003, Biological chemistry.

[14]  C. Garrido.  Size matters: of the small HSP27 and its large oligomers , 2002, Cell Death and Differentiation.

[15]  M. Lotze,et al.  Ceramide Mediates Tumor-Induced Dendritic Cell Apoptosis1 , 2001, The Journal of Immunology.

[16]  S. Loening,et al.  Tumor M2 Pyruvate Kinase in Plasma of Patients with Urological Tumors , 2001, Tumor Biology.

[17]  Ash A. Alizadeh,et al.  Towards a novel classification of human malignancies based on gene expression patterns , 2001, The Journal of pathology.

[18]  H. Friess,et al.  Comparative Analysis of Galectins in Primary Tumors and Tumor Metastasis in Human Pancreatic Cancer , 2001, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[19]  Kanefusa Kato,et al.  Phosphorylation-induced Change of the Oligomerization State of αB-crystallin* , 2001, The Journal of Biological Chemistry.

[20]  J. Mesterharm,et al.  Tumor type M2 pyruvate kinase expression in advanced breast cancer. , 2000, Anticancer research.

[21]  E. Petricoin,et al.  An approach to proteomic analysis of human tumors , 2000, Molecular carcinogenesis.

[22]  S. Narumiya,et al.  Rho-associated Kinase ROCK Activates LIM-kinase 1 by Phosphorylation at Threonine 508 within the Activation Loop* , 2000, The Journal of Biological Chemistry.

[23]  K. Kayser,et al.  Galectins-1 and -3 and their ligands in tumor biology , 1999, Journal of Cancer Research and Clinical Oncology.

[24]  Johannes Buchner,et al.  Regulation of Hsp27 Oligomerization, Chaperone Function, and Protective Activity against Oxidative Stress/Tumor Necrosis Factor α by Phosphorylation* , 1999, The Journal of Biological Chemistry.

[25]  M. Posewitz,et al.  Immobilized gallium(III) affinity chromatography of phosphopeptides. , 1999, Analytical chemistry.

[26]  B. Gilchrest,et al.  The pathogenesis of melanoma induced by ultraviolet radiation. , 1999, The New England journal of medicine.

[27]  M. Jäättelä,et al.  Escaping cell death: survival proteins in cancer. , 1999, Experimental cell research.

[28]  D. Pappin,et al.  The potential use of laser capture microdissection to selectively obtain distinct populations of cells for proteomic analysis — Preliminary findings , 1999, Electrophoresis.

[29]  L. Ramagli.  Quantifying protein in 2-D PAGE solubilization buffers. , 1999, Methods in molecular biology.

[30]  H. Mischinger,et al.  TUM2-PK (pyruvate kinase type tumor M2), CA19-9 and CEA in patients with benign, malignant and metastasizing pancreatic lesions. , 1999, Anticancer research.

[31]  J. Gamel,et al.  Cause-specific versus all-cause survival. , 1998, Ophthalmology.

[32]  Morten Østergaard,et al.  Human and mouse proteomic databases: novel resources in the protein universe , 1998, FEBS letters.

[33]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[34]  E. Campo,et al.  Differential expression of galectin 3 and galectin 1 in colorectal cancer progression. , 1997, Gastroenterology.

[35]  B. Chauffert,et al.  HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs. , 1997, Cancer research.

[36]  Marie-France Carlier,et al.  Actin Depolymerizing Factor (ADF/Cofilin) Enhances the Rate of Filament Turnover: Implication in Actin-based Motility , 1997, The Journal of cell biology.

[37]  P. D. de Jong,et al.  Prognostic parameters in uveal melanoma: a review. , 1996, Survey of ophthalmology.

[38]  R. Lotan,et al.  Expression of galectins in head and neck squamous cell carcinoma , 1996, Head & neck.

[39]  D. Latchman,et al.  Do heat shock proteins have a role in breast cancer? , 1996, British Journal of Cancer.

[40]  S. Spiegel,et al.  Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate , 1996, Nature.

[41]  D. Hochstrasser,et al.  Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. , 1996, Biotechnology & genetic engineering reviews.

[42]  L. Penland,et al.  Use of a cDNA microarray to analyse gene expression patterns in human cancer , 1996, Nature Genetics.

[43]  R. Desnick,et al.  Purification, characterization, and biosynthesis of human acid ceramidase , 1995, The Journal of Biological Chemistry.

[44]  J. Landry,et al.  Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27 , 1995, Molecular and cellular biology.

[45]  R. Bresalier,et al.  Expression of an endogenous galactose-binding lectin correlates with neoplastic progression in the colon. , 1995, Cancer.

[46]  J. Behlke,et al.  Phosphorylation and supramolecular organization of murine small heat shock protein HSP25 abolish its actin polymerization-inhibiting activity. , 1994, The Journal of biological chemistry.

[47]  T. Soussi,et al.  Cancer and the heat shock response. , 1994, European journal of cancer.

[48]  N. Bornfeld,et al.  Prognosis and treatment of disseminated uveal melanoma , 1993, Cancer.

[49]  B. Ames,et al.  Oxidants, antioxidants, and the degenerative diseases of aging. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[50]  J. Gamel,et al.  Biologic distinctions between cure and time to death in 2892 patients with intraocular melanoma , 1993, Cancer.

[51]  K. Sandhoff,et al.  Biosynthesis of sphingolipids: dihydroceramide and not sphinganine is desaturated by cultured cells. , 1992, Biochemical and biophysical research communications.

[52]  C. Anderson,et al.  Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. , 1992, The Journal of biological chemistry.

[53]  C. Nathan,et al.  Production of large amounts of hydrogen peroxide by human tumor cells. , 1991, Cancer research.

[54]  Ashu Sharma,et al.  Role of galaptin in ovarian carcinoma adhesion to extracellular matrix in vitro , 1990, Journal of cellular biochemistry.

[55]  E. Newsholme,et al.  Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. , 1990, The Biochemical journal.

[56]  R. Lotan,et al.  Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents. , 1989, Cancer letters.

[57]  R. Lotan,et al.  Endogenous lectins as mediators of tumor cell adhesion , 1988, Journal of cellular biochemistry.

[58]  R. Glynn,et al.  Epidemiologic aspects of uveal melanoma. , 1988, Survey of ophthalmology.

[59]  J. Alhadeff,et al.  Variant serum β‐hexosaminidase as a biochemical marker of malignancy , 1986 .

[60]  J. Alhadeff,et al.  Variant serum beta-hexosaminidase as a biochemical marker of malignancy. , 1986, Cancer.

[61]  A. Dhillon,et al.  Neurone specific enolase and S100 protein as possible prognostic indicators in melanoma * , 1984, Histopathology.

[62]  P. Lavin,et al.  A prognostic factor study of disease-free interval and survival following enucleation for uveal melanoma. , 1983, Archives of ophthalmology.

[63]  J. Royds,et al.  Enolase isoenzymes in uveal melanomas--a possible parameter of malignancy. , 1983, The British journal of ophthalmology.

[64]  A. Raz,et al.  Lectin-like activities associated with human and murine neoplastic cells. , 1981, Cancer research.