This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alonso, S. R. Articles by Rodríguez-Peralto, J. L. Search for Related Content PubMed PubMed Citation Articles by Alonso, S. R. Articles by Rodríguez-Peralto, J. L.

A High-Throughput Study in Melanoma Identifies Epithelial-Mesenchymal Transition as a Major Determinant of Metastasis

¹ Molecular Pathology Programme and ² Histology and Immunohistochemistry Unit, Centro Nacional de Investigaciones Oncológicas; Departments of ³ Pathology and ⁴ Dermatology, Hospital Universitario 12 de Octubre; ⁵ Centro Nacional de Epidemiología, Instituto de Salud Carlos III, Madrid, Spain; and Departments of ⁶ Pathology and ⁷ Dermatology, Hospital Universitario San Cecilio, Granada, Spain

Requests for reprints: Miguel A. Piris, Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas, C/Melchor Fernández Almagro 3, Madrid 28029, Spain. Phone: 34-91-224-69-00; Fax: 34-91-224-69-23; E-mail: mapiris{at}cnio.es.

Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets. [Cancer Res 2007;67(7):3450–60]

This article has been cited by other articles:

				Y. Liu, F. Ye, Q. Li, S. Tamiya, D. S. Darling, H. J. Kaplan, and D. C. Dean Zeb1 Represses Mitf and Regulates Pigment Synthesis, Cell Proliferation, and Epithelial Morphology Invest. Ophthalmol. Vis. Sci., November 1, 2009; 50(11): 5080 - 5088. [Abstract] [Full Text] [PDF]

				S. Das, L. G. Harris, B. J. Metge, S. Liu, A. I. Riker, R. S. Samant, and L. A. Shevde The Hedgehog Pathway Transcription Factor GLI1 Promotes Malignant Behavior of Cancer Cells by Up-regulating Osteopontin J. Biol. Chem., August 21, 2009; 284(34): 22888 - 22897. [Abstract] [Full Text] [PDF]

				B. E. G. Rothberg, M. B. Bracken, and D. L. Rimm Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis J Natl Cancer Inst, April 1, 2009; 101(7): 452 - 474. [Abstract] [Full Text] [PDF]

				M. Parri, M. L. Taddei, F. Bianchini, L. Calorini, and P. Chiarugi EphA2 Reexpression Prompts Invasion of Melanoma Cells Shifting from Mesenchymal to Amoeboid-like Motility Style Cancer Res., March 1, 2009; 69(5): 2072 - 2081. [Abstract] [Full Text] [PDF]

				H. Grinberg-Rashi, E. Ofek, M. Perelman, J. Skarda, P. Yaron, M. Hajduch, J. Jacob-Hirsch, N. Amariglio, M. Krupsky, D. A. Simansky, et al. The Expression of Three Genes in Primary Non-Small Cell Lung Cancer Is Associated with Metastatic Spread to the Brain Clin. Cancer Res., March 1, 2009; 15(5): 1755 - 1761. [Abstract] [Full Text] [PDF]

				J. W.J. van Kilsdonk, R. H. Wilting, M. Bergers, G. N.P. van Muijen, J. Schalkwijk, L. C.L.T. van Kempen, and G. W.M. Swart Attenuation of Melanoma Invasion by a Secreted Variant of Activated Leukocyte Cell Adhesion Molecule Cancer Res., May 15, 2008; 68(10): 3671 - 3679. [Abstract] [Full Text] [PDF]

				C. K. Augustine, Y. Yoshimoto, M. Gupta, P. A. Zipfel, M. A. Selim, P. Febbo, A. M. Pendergast, W. P. Peters, and D. S. Tyler Targeting N-Cadherin Enhances Antitumor Activity of Cytotoxic Therapies in Melanoma Treatment Cancer Res., May 15, 2008; 68(10): 3777 - 3784. [Abstract] [Full Text] [PDF]

				G. M. Kreizenbeck, A. J. Berger, A. Subtil, D. L. Rimm, and B. E. Gould Rothberg Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 949 - 958. [Abstract] [Full Text] [PDF]