Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines CXCL5/CXC ligand (CXCL) 5 and interleukin-8/CXCL8 in Human Non-Small cell lung cancer

ArticleinCancer Research 64(5):1853-60 · April 2004with27 Reads
Impact Factor: 9.33 · DOI: 10.1158/0008-5472.CAN-03-3262 · Source: PubMed

    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.