Stathopoulos Georgios T, Zhu Zhiwen, Everhart M Brett, Kalomenidis Ioannis, Lawson William E, Bilaceroglu Semra, Peterson Todd E, Mitchell Daphne, Yull Fiona E, Light Richard W, Blackwell Timothy S
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T-1218 MCN, Nashville, TN 37232-2650, USA.
Am J Respir Cell Mol Biol. 2006 Feb;34(2):142-50. doi: 10.1165/rcmb.2005-0130OC. Epub 2005 Oct 6.
We developed a novel mouse model of malignant pleural effusion (MPE) by injecting Lewis lung cancer (LLC) cells directly into the pleural space of syngeneic C57B/6 mice. The pleural effusions in this model share common cellular and biochemical features with human MPEs. Implantation and growth of pleural tumors triggers a host inflammatory response characterized by a mixed inflammatory cell influx into the pleural fluid. LLC cells exhibited high basal nuclear factor (NF)-kappaB activity in vitro and in vivo, which we used to drive expression of a NF-kappaB-dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-kappaB-dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-kappaB in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-kappaB inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF-alpha levels. These studies indicate that tumor NF-kappaB activity regulates pleural tumor progression. This reproducible model of MPE can be used to further study the influence of specific host and tumor factors on the pathogenesis of MPE and evaluate new therapeutic strategies.
我们通过将Lewis肺癌（LLC）细胞直接注射到同基因C57B/6小鼠的胸腔内，建立了一种新型恶性胸腔积液（MPE）小鼠模型。该模型中的胸腔积液与人类MPE具有共同的细胞和生化特征。胸腔肿瘤的植入和生长引发了宿主炎症反应，其特征是混合性炎症细胞流入胸腔积液。LLC细胞在体外和体内均表现出高基础核因子（NF）-κB活性，我们利用该活性驱动NF-κB依赖性绿色荧光蛋白-萤火虫荧光素酶融合报告基因构建体的表达。NF-κB依赖性报告基因表达允许对胸腔肿瘤进行活体追踪。抑制LLC细胞中的NF-κB并不影响培养中的细胞活力；然而，注射表达显性NF-κB抑制剂的LLC细胞导致肿瘤负荷降低、胸腔积液体积减少以及胸腔积液TNF-α水平降低。这些研究表明肿瘤NF-κB活性调节胸腔肿瘤进展。这种可重复的MPE模型可用于进一步研究特定宿主和肿瘤因素对MPE发病机制的影响，并评估新的治疗策略。
