Lysyl oxidase expression and inhibition in uveal melanoma

Lysyl oxidase expression and inhibition in uveal melanoma

Author Abourbih, Daniel A. Google Scholar
Di Cesare, Sebastian Google Scholar
Orellana, Maria E. Google Scholar
Antecka, Emilia Google Scholar
Martins, Claudia Google Scholar
Petruccelli, Luca A. Google Scholar
Burnier, Miguel N. Autor UNIFESP Google Scholar
Institution McGill Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract 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. Melanoma Res 20:97-106 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
Keywords beta-aminopropionitrile
cobalt chloride
invasion
hypoxia
lysyl oxidase
proliferation
uveal melanoma
Language English
Sponsor Cedars Cancer Institute
Date 2010-04-01
Published in Melanoma Research. Philadelphia: Lippincott Williams & Wilkins, v. 20, n. 2, p. 97-106, 2010.
ISSN 0960-8931 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 97-106
Origin http://dx.doi.org/10.1097/CMR.0b013e328336edfe
Access rights Closed access
Type Article
Web of Science ID WOS:000276239400004
URI http://repositorio.unifesp.br/handle/11600/32444

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