Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer
Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer
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DOI：
10.1159/000446244
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发表时间：
2016-01-01
期刊：
影响因子：
5
通讯作者：
Freitas, Vanessa Morals
中科院分区：
文献类型：
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作者：
Lima, Maira Assis;dos Santos, Liliane;Freitas, Vanessa Morals
背景：ADAMTS是具有去整合素和血小板反应素基序的金属蛋白酶。它们是分泌的蛋白酶，在炎症、血管生成和泌尿生殖发育等生物学过程中发挥作用。ADAMTS具有特异性底物，如蛋白聚糖（PG）多功能蛋白聚糖、聚集蛋白聚糖和短蛋白聚糖。尽管有数据表明ADAMTS在肿瘤侵袭和转移中的作用，但这些分子在癌症进展中的作用仍然存在争议。在卵巢癌中，ADAMTS基因突变的重要性最近被描述并与化疗结果相关。目的：分析ADAMTS-1、ADAMTS-4、ADAMTS-5和TIMP-3在卵巢良性、交界性和恶性肿瘤中的表达。我们还评估了ADAMTS底物聚集蛋白聚糖、短蛋白聚糖和多功能蛋白聚糖在这些肿瘤中的表达。总生存率和蛋白表达之间的相关性进行了研究。方法：肿瘤按WHO女性生殖器官肿瘤分类标准进行分类。免疫组化法检测PG蛋白表达。通过染色区域的百分比测量分析标记差异。结果：ADAMTS-1、ADAMTS-5及其组织抑制剂TIMP-3在交界性肿瘤和恶性肿瘤中表达高于良性肿瘤。与良性卵巢癌相比，恶性亚型中聚集蛋白聚糖和多功能蛋白聚糖水平升高。ADAMTS-1、TIMP-3和多功能蛋白聚糖的高表达与较短的总生存期相关。结论：蛋白酶，TIMP-3和底物表达的比较表明，在恶性肿瘤中，所有ADAMTS和TIMP-3的表达水平显着提高相比，研究的底物。(C)2016 S. Karger AG，巴塞尔
Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied. (C) 2016 S. Karger AG, Basel