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.
Põld
Mehis
M
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.
Zhu
Li X
LX
Sharma
Sherven
S
Burdick
Marie D
MD
Lin
Ying
Y
Lee
Peter P N
PP
Põld
Anu
A
Luo
Jie
J
Krysan
Kostyantyn
K
Dohadwala
Mariam
M
Mao
Jenny T
JT
Batra
Raj K
RK
Strieter
Robert M
RM
Dubinett
Steven M
SM
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