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 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.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095, USA.
Mehis
M
Põld
Li X
LX
Zhu
Sherven
S
Sharma
Marie D
MD
Burdick
Ying
Y
Lin
Peter P N
PP
Lee
Anu
A
Põld
Jie
J
Luo
Kostyantyn
K
Krysan
Mariam
M
Dohadwala
Jenny T
JT
Mao
Raj K
RK
Batra
Robert M
RM
Strieter
Steven M
SM
Dubinett
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000737:chemistry / Q000188:drug therapy; D045744:Cell Line, Tumor; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000032:analysis*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008175:Lung Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000188:drug therapy; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; C094739:Cxcl5 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone