High PTP4A3 Phosphatase Expression Correlates with Metastatic Risk in Uveal Melanoma Patients

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-02, Vol.71 (3), p.666-674
• Main Authors: LAURENT, Cécile, VALET, Fabien, RAPINAT, Audrey, GENTIEN, David, COUTURIER, Jérôme, SASTRE-GARAU, Xavier, DESJARDINS, Laurence, THIERY, Jean-Paul, ROMAN-ROMAN, Sergio, ASSELAIN, Bernard, BARILLOT, Emmanuel, PIPERNO-NEUMANN, Sophie, PLANQUE, Nathalie, SAULE, Simon, SILVERI, Licia, MAACHA, Selma, ANEZO, Océane, HUPE, Philippe, PLANCHER, Corine, REYES, Cécile, ALBAUD, Benoit
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Chick Embryo; Chromosomes, Human, Pair 8; Eye Enucleation; Female; Gene Expression; Humans; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Male; Medical sciences; Melanoma - enzymology; Melanoma - genetics; Melanoma - pathology; Melanoma - surgery; Middle Aged; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Ophthalmology; Pharmacology. Drug treatments; Protein Tyrosine Phosphatases - biosynthesis; Protein Tyrosine Phosphatases - genetics; Survival Rate; Tumors; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Uveal Neoplasms - enzymology; Uveal Neoplasms - genetics; Uveal Neoplasms - pathology; Uveal Neoplasms - surgery
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-10-0605

A high percentage of uveal melanoma patients develop metastatic tumors predominantly in the liver. We studied the molecular profiles derived from gene expression microarrays and comparative genomic hybridization microarrays, to identify genes associated with metastasis in this aggressive cancer. We compared 28 uveal melanomas from patients who developed liver metastases within three years of enucleation with 35 tumors from patients without metastases or who developed metastases more than 3 years after enucleation. Protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL3), was identified as a strong predictor of metastasis occurrence. We demonstrated that the differential expression of this gene, which maps to 8q24.3, was not merely a consequence of 8q chromosome overrepresentation. PTP4A3 overexpression in uveal melanoma cell lines significantly increased cell migration and invasiveness in vivo, suggesting a direct role for this protein in metastasis. Our findings suggest that PTP4A3 or its cellular substrates could constitute attractive therapeutic targets to treat metastatic uveal melanomas.