Cyclooxygenase-2 dependent expression of angiogenic CXC chemokines, ENA-78/CXCL5 and IL-8/CXCL8, in human non-small cell lung cancer

4942 Elevated tumor cyclooxygenase 2 (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, CXCL8 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 in vitro production of both peptides. Consistent with the COX-2 in vitro effects, the enhanced tumor growth of COX-2 expressing tumors in a SCID-mouse model of NSCLC was accompanied by elevated levels of CXCL5 and CXCL8. Furthermore, neutralizing anti-CXCL5 and anti-CXCL8 antisera inhibited the tumor growth of COX-2 overexpressing tumors in SCID-mice. In addition, the COX-2 related angiogenic capacity of H157 was efficiently reduced by anti-CXCR2 treatment in a rat corneal pocket model of angiogenesis. In summary, we conclude that COX-2 contributes to the progression of NSCLC tumorigenesis by enhancing the expression of angiogenic chemokines CXCL8 and CXCL5. Further studies will be required to determine if COX-2 inhibitors can regulate angiogenic chemokines in lung cancer patients.