Lysyl oxidase: A potential modulator of early events in the uveal melanoma metastatic cascade

LOX is a marker of poor prognosis in several malignancies and is hypothesized to promote a migratory phenotype in hypoxic breast carcinomas. This thesis aims to characterize the expression of LOX and LOXL2 in human UM and to evaluate the transcriptional control of LOX under simulated hypoxic conditi...

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Bibliographic Details
Main Author Abourbih, Daniel Asher
Format Dissertation
LanguageEnglish
Published ProQuest Dissertations & Theses 01.01.2009
Subjects
Oncology
Ophthalmology
Pathology
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Summary:LOX is a marker of poor prognosis in several malignancies and is hypothesized to promote a migratory phenotype in hypoxic breast carcinomas. This thesis aims to characterize the expression of LOX and LOXL2 in human UM and to evaluate the transcriptional control of LOX under simulated hypoxic conditions. DPA and BAPN, both LOX catalytic inhibitors, were used to evaluate the effect of inhibiting this enzyme on cellular proliferation and invasion. Eighty-one percent of FFPE samples stained positive for LOX. High LOX expression correlated with the aggressive epithelioid cell type and was associated with shorter metastasis-free survival. Simulated hypoxia resulted in a significant increase in LOX mRNA expression likely mediated by HIF-1• transcriptional promotion. Inhibiting LOX’s catalytic activity significant reduced cellular invasion but had no effect on cell proliferation. These findings suggest that LOX may facilitate the escape of malignant cells from the eye following the development of tissue hypoxia.
ISBN:9780494615287
0494615281