Institut Curie, Paris, France.
Cancer Res. 2011 Feb 1;71(3):666-74. doi: 10.1158/0008-5472.CAN-10-0605. Epub 2010 Dec 6.
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.
葡萄膜黑色素瘤患者中很大一部分会发生肝转移为主的转移性肿瘤。我们通过基因表达微阵列和比较基因组杂交微阵列分析，研究了源自这些侵袭性癌症的分子谱，以确定与转移相关的基因。我们比较了 28 例在眼球摘除后三年内发生肝转移的葡萄膜黑色素瘤患者和 35 例无转移或在眼球摘除后 3 年以上发生转移的患者的肿瘤。蛋白酪氨酸磷酸酶 IVA 成员 3（PTP4A3/PRL3）被鉴定为转移发生的强预测因子。我们证明，该基因位于 8q24.3 上，其差异表达不仅是 8q 染色体过表达的结果。在葡萄膜黑色素瘤细胞系中过表达 PTP4A3 可显著增加体内细胞迁移和侵袭能力，提示该蛋白在转移中起直接作用。我们的研究结果表明，PTP4A3 或其细胞底物可能成为治疗转移性葡萄膜黑色素瘤的有吸引力的治疗靶点。
