Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer

Elevated tumor cyclooxygenase (COX)-2 activity plays a multifaceted role in non-small cell lung cancer (NSCLC). To elucidate the role of COX-2 in the in vitro and in vivo expression of two known NSCLC angiogenic peptides, CXC ligand (CXCL) 8 and CXCL5, we studied two COX-2 gene-modified NSCLC cell l...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-03, Vol.64 (5), p.1853-1860
Main Authors: FOLD, Mehis, ZHU, Li X, MAO, Jenny T, BATRA, Raj K, STRIETER, Robert M, DUBINETT, Steven M, SHARMA, Sherven, BURDICK, Marie D, YING LIN, LEE, Peter P. N, POLD, Anu, JIE LUO, KRYSAN, Kostyantyn, DOHADWALA, Mariam
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Animals
Antineoplastic agents
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - blood supply
Carcinoma, Non-Small-Cell Lung - chemistry
Carcinoma, Non-Small-Cell Lung - drug therapy
Cell Line, Tumor
Chemokine CXCL5
Chemokines, CXC - analysis
Cyclooxygenase 2
Dinoprostone - physiology
Humans
Intercellular Signaling Peptides and Proteins - analysis
Isoenzymes - antagonists & inhibitors
Isoenzymes - physiology
Lung Neoplasms - blood supply
Lung Neoplasms - chemistry
Lung Neoplasms - drug therapy
Medical sciences
Membrane Proteins
Mice
Mice, SCID
Neovascularization, Pathologic - etiology
NF-kappa B - metabolism
Pharmacology. Drug treatments
Prostaglandin-Endoperoxide Synthases - physiology
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Elevated tumor cyclooxygenase (COX)-2 activity plays a multifaceted role in non-small cell lung cancer (NSCLC). To elucidate the role of COX-2 in the in vitro and in vivo expression of two known NSCLC angiogenic peptides, CXC ligand (CXCL) 8 and CXCL5, we studied two COX-2 gene-modified NSCLC cell lines, A549 and H157. COX-2 overexpression enhanced the in vitro expression of both CXCL8 and CXCL5. In contrast, specific COX-2 inhibition decreased the production of both peptides as well as nuclear translocation of nuclear factor kappaB. In a severe combined immunodeficient mouse model of human NSCLC, the enhanced tumor growth of COX-2-overexpressing tumors was inhibited by neutralizing anti-CXCL5 and anti-CXCL8 antisera. We conclude that COX-2 contributes to the progression of NSCLC tumorigenesis by enhancing the expression of angiogenic chemokines CXCL8 and CXCL5.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-03-3262