Heterogeneous expression of cyclooxygenase-2 and inducible nitric oxide synthase within colorectal tumors: Correlation with tumor angiogenesis
Heterogeneous expression of cyclooxygenase-2 and inducible nitric oxide synthase within colorectal tumors: Correlation with tumor angiogenesis
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DOI：
10.1016/j.dld.2009.04.010
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发表时间：
2010-01-01
影响因子：
4.5
通讯作者：
Masini, E.
中科院分区：
文献类型：
--
作者：
Cianchi, F.;Cuzzocrea, S.;Masini, E.
目的：探讨环氧合酶-2(COX-2)和诱导型一氧化氮合酶(INOS)在结直肠癌不同部位的表达/活性是否存在差异，并分析其与肿瘤血管生成的关系。方法：检测46例结直肠癌组织中微血管密度(MVD)和COX-2、iNOS、血管内皮生长因子(VEGF)及其受体-2(VEGFR-2)蛋白的表达。结果：IF中COX-2和iNOS蛋白表达及活性均显著高于TC。同样，从TC到IF，MVD和VEGF/VEGFR-2的表达显著增加。只有COX-2在TC和IF中的表达与MVD和VEGF/VEGFR-2的表达显著相关。结论：COX-2和iNOS在结直肠癌中存在异质性表达。在IF处COX-2的上调与血管密度和VEGF/VEGFR-2表达的增加相平行，从而支持了肿瘤外围是结直肠癌最具侵袭性的部分的假设。(C)2009年《意大利胃肠病学杂志》。爱思唯尔有限公司出版。保留所有权利。
Background: Recent studies have shown that the cyclooxygenase (COX) and the inducible nitric oxide synthase (iNOS) pathways are involved in the development of tumor angiogenesis in human cancers.Aims: To investigate whether a different pattern of COX-2 and iNOS expression/activity exists within different areas of colorectal tumors and to analyze the relationship between these two enzymes and tumor angiogenesis.Methods: Microvessel density (MVD) and COX-2, iNOS, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein expression were evaluated at both the invasive front (IF) and the tumor center (TC) in 46 human colorectal cancer specimens. We also investigated the concentration of PGE(2) and NO at the same sites.Results: COX-2 and iNOS protein expression and activity were significantly higher within the IF than the TC of the tumor specimens. Similarly, MVD and VEGF/VEGFR-2 expression significantly increased from the TC to the IF. Only COX-2 expression was significantly correlated with MVD and VEGF/VEGFR-2 expression at both the TC and the IF.Conclusion: Our study shows a heterogeneous expression of COX-2 and iNOS in colorectal cancer. The up-regulation of COX-2 at the IF parallels an increase in vessel density and VEGF/VEGFR-2 expression, thus supporting the hypothesis that the tumor periphery is the most aggressive portion of a colorectal tumor. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.