Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44

被引:196
作者
Dohadwala, M
Luo, J
Zhu, L
Lin, Y
Dougherty, GJ
Sharma, S
Huang, M
Pold, N
Batra, RK
Dubinett, SM
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Radiat Oncol, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA
[3] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA
关键词
D O I
10.1074/jbc.C100140200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Elevated tumor cyclooxygenase (COX-2) expression is associated with increased angiogenesis, tumor invasion, and suppression of host immunity. We have previously shown that genetic inhibition of tumor COX-2 expression reverses the immunosuppression induced by nonsmall cell lung cancer (NSCLC). To assess the impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were transduced with a retroviral vector expressing the human COX-2 cDNA in the sense (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S clones expressed significantly more COX-2 protein, produced 10-fold more prostaglandin E-2, and demonstrated an enhanced invasive capacity compared with control vector-transduced or parental cells. CD44, the cell surface receptor for hyaluronate, was overexpressed in COX-2-S cells, and specific blockade of CD44 significantly decreased tumor cell invasion. In contrast, COX-2-AS clones had a very limited capacity for invasion and showed diminished expression of CD44. These findings suggest that a COX-2-mediated, CD44-dependent pathway is operative in NSCLC invasion. Because tumor COX-2 expression appears to have a multifaceted role in conferring the malignant phenotype, COX-2 may be an important target for gene or pharmacologic therapy in NSCLC.
引用
收藏
页码:20809 / 20812
页数:4
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