Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Active Transport, Cell Nucleus
-
Animals
-
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
-
Membrane Proteins
-
Mice
-
Mice, SCID
-
NF-kappa B / metabolism
-
Neovascularization, Pathologic / etiology
-
Prostaglandin-Endoperoxide Synthases / physiology*
Substances
-
CXCL5 protein, human
-
Chemokine CXCL5
-
Chemokines, CXC
-
Cxcl5 protein, mouse
-
Intercellular Signaling Peptides and Proteins
-
Isoenzymes
-
Membrane Proteins
-
NF-kappa B
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Prostaglandin-Endoperoxide Synthases
-
Dinoprostone