Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma
| Autor: | A J, Marrogi, W D, Travis, J A, Welsh, M A, Khan, H, Rahim, H, Tazelaar, P, Pairolero, V, Trastek, J, Jett, N E, Caporaso, L A, Liotta, C C, Harris |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Cytoplasm Lymphokines Lung Neoplasms Neovascularization Pathologic Vascular Endothelial Growth Factors Microcirculation Smoking Membrane Proteins Endothelial Growth Factors Immunohistochemistry Disease-Free Survival Isoenzymes Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Carcinoma Non-Small-Cell Lung Lymphatic Metastasis Humans Female Nitric Oxide Synthase |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 6(12) |
| ISSN: | 1078-0432 |
| Popis: | 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 (Por = 0.001). More adenocarcindmas and large cell carcinomas displayed overexpression of NOS2 when compared with squamous cell carcinoma (SCC; r = 0.44; P0.001). NOS2 and COX2 levels were found to correlate positively with VEGF status (r = 0.44; P0.001, 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. |
| Databáze: | OpenAIRE |
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