Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma.
Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma.
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发表时间：
2000-12
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通讯作者：
A. Marrogi;W. Travis;J. Welsh;Mohammed A. Khan;H. Rahim;H. Tazelaar;P. Pairolero;V. Trastek;J. Jett;N. Caporaso;L. Liotta;C. Harris
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作者：
A. Marrogi;W. Travis;J. Welsh;Mohammed A. Khan;H. Rahim;H. Tazelaar;P. Pairolero;V. Trastek;J. Jett;N. Caporaso;L. Liotta;C. Harris
我们研究了一氧化氮合酶（NOS 2）、环氧合酶-2（COX 2）和血管内皮生长因子（VEGF）蛋白水平分别与人非小细胞肺癌（NSCLC）的微血管密度（MVD）和临床结局直接相关的假设。此外，我们假设MVD可以解释某些组织学肺癌亚型通过血液学途径早期转移的倾向。免疫组化方法检测106例手术切除的NSCLC标本中NOS 2、COX 2和VEGF的蛋白表达水平，并通过计数CD 31反应性血管（BV）检测MVD。NOS 2、COX 2和VEGF的免疫反应性分别在48%、48%和58%的研究对象中观察到，并且它们的水平与肿瘤-间质间期的MVD相关（P <或= 0.001）。NOS 2在腺癌和大细胞癌中的表达明显高于鳞癌（r = 0.44，P < 0.001）。NOS 2和COX 2水平与VEGF状态呈正相关（r = 0.44; P分别< 0.001、0.01和0.03）。这些结果证实了这些因子在NSCLC血管生成中的显著相互作用。尽管血管生成因子和MVD均与患者生存率无关，但后者与鳞状（SCC; 73 BV/mm 2）和非SCC（78 BV/mm 2）肿瘤的临床分期相关。这些结果表明，血管生成是一个复杂的过程，涉及多种因素，包括NOS 2，COX 2和VEGF。此外，血管生成在各种组织学肺癌类型的生物学中的作用可能是不同的。血管生成的复杂性可以解释在靶向单一蛋白质的抗血管生成治疗中观察到的适度结果。
We have investigated the hypothesis that nitric oxide synthase (NOS2), cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) protein levels individually demonstrate a direct correlation with microvessel density (MVD) and clinical outcome in human non-small cell lung cancer (NSCLC). Furthermore, we hypothesized that MVD may explain the propensity of certain histological lung cancer subtypes for early metastasis via a hematological route. Immunohistochemically, we studied the protein expression levels of NOS2, COX2, and VEGF and MVD by counting CD31-reactive blood vessels (BVs) in 106 surgically resected NSCLC specimens. NOS2, COX2, and VEGF immunoreactivity were observed in 48, 48, and 58%, respectively, of the study subjects, and their levels correlated with MVD at the tumor-stromal interphase (P < or = 0.001). More adenocarcindmas and large cell carcinomas displayed overexpression of NOS2 when compared with squamous cell carcinoma (SCC; r = 0.44; P < 0.001). NOS2 and COX2 levels were found to correlate positively with VEGF status (r = 0.44; P < 0.001, 0.01, and 0.03, respectively). These results attest to the significant interaction of these factors in the angiogenesis of NSCLC. Although neither angiogenic factors nor MVD correlated with patient survival, the latter correlated with tumor clinical stage in both squamous (SCC; 73 BVs/mm2) and non-SCC (78 BVs/mm2) tumors. These results indicate that angiogenesis is a complex process that involves multiple factors including NOS2, COX2, and VEGF. Furthermore, the role of angiogenesis in the biology of various histological lung cancer types may be different. The complexity of angiogenesis may explain the modest results observed in antiangiogenesis therapy that target a single protein.