Nitric Oxide Synthase, Cyclooxygenase 2, and Vascular Endothelial Growth Factor in the Angiogenesis of Non-Small Cell Lung Carcinoma
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)....
Saved in:
Published in | Clinical cancer research Vol. 6; no. 12; pp. 4739 - 4744 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.12.2000
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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 ≤ 0.001). More adenocarcinomas 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/mm 2 ) and
non-SCC (78 BVs/mm 2 ) 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. |
---|---|
ISSN: | 1078-0432 1557-3265 |