Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous ovarian cancer
Uncovering the role of nuclear Lysyl oxidase (LOX) in advanced high grade serous ovarian cancer
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DOI：
10.1016/j.ygyno.2017.05.001
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发表时间：
2017-07-01
影响因子：
4.7
通讯作者：
Gallo, Daniela
中科院分区：
文献类型：
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作者：
De Donato, Marta;Petrillo, Marco;Gallo, Daniela
目标。赖氨酰氧化酶(LOX)是一种催化细胞外基质中的胶原和弹性蛋白交联的酶，从而控制组织的抗张强度。除了这一主要功能外，有证据支持LOX在许多关键的生物学功能中发挥作用，包括基因表达调节、细胞生长、黏附和迁移。因此，最近的研究已经支持LOX在癌症进展和转移中的关键作用。本研究旨在探讨细胞内LOX在卵巢癌中的预后意义和功能作用。为此，我们用免疫组织化学方法分析了70例晚期高级别浆液性卵巢癌(HGSOC)患者存档肿瘤材料中LOX的表达，并分析了LOX表达与临床病理参数和化疗反应的相关性。体外实验还研究了LOX表达对HGSOC细胞行为方面的功能影响。我们的结果表明，在晚期HGSOC中，核LOX表达与不良预后相关，是疾病复发的独立预后因素。此外，高核素水平被认为与一线化疗耐药有关。通过HGSOC细胞系的基因表达调控实验，我们证明LOX对细胞的增殖、迁移和锚定非依赖性生长具有正向调节作用。总而言之，我们的数据表明LOX在HGSOC中作为肿瘤促进剂发挥作用，并积极调节转移级联的几个方面。(C)2017 Elsevier Inc.保留所有权利。
Objective. Lysyl oxidase (LOX) is an enzyme that catalyzes the cross-linking of collagen and elastin in the extracellular matrix, thus controlling the tensile strength of tissues. Along with this primary function, there are evidences supporting a role for LOX in many critical biological functions, including gene expression regulation, cell growth, adhesion and migration. Accordingly, recent studies have supported a pivotal role for LOX in cancer progression and metastasis. The current study aimed at investigating the prognostic significance and the functional role of intracellular LOX in ovarian cancer.Methods. To this end, we analyzed LOX expression by immunohistochemistry in archived tumor material from advanced high grade serous ovarian cancer (HGSOC) patients (n = 70) and correlated data with clinicopathological parameters and with response to chemotherapy. In vitro experiments were also used to investigate the functional consequences of LOX expression on behavioral aspects of HGSOC cells.Results. Our results showed that nuclear LOX expression is associated with unfavorable outcome in advanced HGSOC, being an independent prognostic factor for disease recurrence. Besides, high nuclear levels were seen to be associated with resistance to first-line chemotherapy. Through gene expression modulation experiments in HGSOC cell lines, we demonstrate that LOX positively regulates cell proliferation, migration and anchorage-independent growth.Conclusions. Collectively, our data suggest that LOX functions as a tumor promoter in HGSOC and positively regulates several aspects of the metastatic cascade. (C) 2017 Elsevier Inc. All rights reserved.