The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, Montreal, PQ, Canada.
Melanoma Res. 2010 Apr;20(2):97-106. doi: 10.1097/CMR.0b013e328336edfe.
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.
赖氨酰氧化酶是几种恶性肿瘤预后不良的标志物，据推测它能促进低氧乳腺癌的迁移表型。本研究旨在通过免疫组织化学方法，分析赖氨酰氧化酶和赖氨酰氧化酶样蛋白在人眼葡萄膜黑色素瘤细胞系和存档脉络膜黑色素瘤中的表达。还将使用氯化钴模拟缺氧条件，研究赖氨酰氧化酶的转录控制。最后，用赖氨酰氧化酶催化抑制剂β-氨基丙腈处理细胞系后，评估细胞增殖和侵袭的变化。对原发性人眼葡萄膜黑色素瘤中赖氨酰氧化酶表达的回顾性分析显示，82%（33 例中的 27 例）的肿瘤呈阳性染色。高赖氨酰氧化酶表达与侵袭性上皮样细胞类型相关，并与无转移生存时间较短相关。模拟缺氧导致赖氨酰氧化酶 mRNA 表达显著增加。抑制赖氨酰氧化酶的催化活性显著降低了细胞侵袭，但对细胞增殖没有影响。本研究首次显示赖氨酰氧化酶在原发性脉络膜黑色素瘤中的表达。这种蛋白可能代表一种潜在的治疗靶点，值得在这种恶性肿瘤中进一步研究。
