Lysyl oxidase expression and inhibition in uveal melanoma.
Lysyl oxidase is a marker of poor prognosis in several malignancies and is hypothesized to promote a migratory phenotype in hypoxic breast carcinomas. This study aims to characterize the expression of the lysyl oxidase and lysyl oxidase-like proteins in human uveal melanoma cell lines and archival choroidal melanomas using immunohistochemistry. The transcriptional control of lysyl oxidase will also be investigated under simulated hypoxic conditions using cobalt chloride. Lastly, changes in cellular proliferation and invasion will be assessed after the treatment of cell lines with beta-aminopropionitrile, a lysyl oxidase catalytic inhibitor. Retrospective analysis of lysyl oxidase expression in primary human uveal melanoma showed 82% (27 of 33) of tumors being stained positive. High lysyl oxidase expression correlated with the aggressive epithelioid cell type and was associated with shorter metastasis-free survival. Simulated hypoxia resulted in a significant increase in lysyl oxidase mRNA expression. Inhibiting lysyl oxidase's catalytic activity significantly reduced cellular invasion but had no effect on cell proliferation. Our study is the first to show lysyl oxidase expression in primary choroidal melanomas. This protein may represent a potential therapeutic target that warrants further study in this malignancy.
Abourbih
Daniel A
DA
The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, Montreal, PQ, Canada. daniel.abourbih@mail.mcgill.ca
Di Cesare
Sebastian
S
Orellana
Maria E
ME
Antecka
Emilia
E
Martins
Claudia
C
Petruccelli
Luca A
LA
Burnier
Miguel N
MN
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014604:Uveal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology
D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human; D008249:Protein-Lysine 6-Oxidase