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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.

Authors
  • Põld, Mehis
  • Zhu, Li X
  • Sharma, Sherven
  • Burdick, Marie D
  • Lin, Ying
  • Lee, Peter P N
  • Põld, Anu
  • Luo, Jie
  • Krysan, Kostyantyn
  • Dohadwala, Mariam
  • Mao, Jenny T
  • Batra, Raj K
  • Strieter, Robert M
  • Dubinett, Steven M
Type
Published Article
Journal
Cancer research
Publication Date
Mar 01, 2004
Volume
64
Issue
5
Pages
1853–1860
Identifiers
PMID: 14996749
Source
Medline
License
Unknown

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.

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