High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients.
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.
Institut Curie, Paris, France.
Cécile
C
Laurent
Fabien
F
Valet
Nathalie
N
Planque
Licia
L
Silveri
Selma
S
Maacha
Océane
O
Anezo
Philippe
P
Hupe
Corine
C
Plancher
Cécile
C
Reyes
Benoit
B
Albaud
Audrey
A
Rapinat
David
D
Gentien
Jérôme
J
Couturier
Xavier
X
Sastre-Garau
Laurence
L
Desjardins
Jean-Paul
JP
Thiery
Sergio
S
Roman-Roman
Bernard
B
Asselain
Emmanuel
E
Barillot
Sophie
S
Piperno-Neumann
Simon
S
Saule
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002642:Chick Embryo; D002898:Chromosomes, Human, Pair 8; D015353:Eye Enucleation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000098943:Uveal Melanoma
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases