环氧化酶-2依赖性血管生成CXC趋化因子ENA-78/CXC配体（CXCL）5和白细胞介素-8/CXCL8在人非小细胞肺癌中的表达

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.

作者信息

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

机构信息

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.

出版信息

Cancer Res. 2004 Mar 1;64(5):1853-60. doi: 10.1158/0008-5472.can-03-3262.

DOI:10.1158/0008-5472.can-03-3262

PMID:14996749

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.

摘要

肿瘤中环氧化酶（COX）-2活性升高在非小细胞肺癌（NSCLC）中发挥多方面作用。为阐明COX-2在两种已知的NSCLC血管生成肽CXC配体（CXCL）8和CXCL5的体外和体内表达中的作用，我们研究了两种COX-2基因修饰的NSCLC细胞系A549和H157。COX-2过表达增强了CXCL8和CXCL5的体外表达。相反，特异性COX-2抑制降低了这两种肽的产生以及核因子κB的核转位。在人NSCLC的严重联合免疫缺陷小鼠模型中，中和抗CXCL5和抗CXCL8抗血清可抑制COX-2过表达肿瘤的增强肿瘤生长。我们得出结论，COX-2通过增强血管生成趋化因子CXCL8和CXCL5的表达促进NSCLC肿瘤发生的进展。