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Nuclear Factor-B Affects Tumor Progression in a Mouse Model of Malignant Pleural Effusion

Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Department of Cell and Developmental Biology, and Department of Cancer Biology, Vanderbilt University School of Medicine; Department of Veterans Affairs, VA Tennessee Valley Healthcare System; Department of Radiology and Radiological Sciences, Vanderbilt Institute of Imaging Science; Pulmonary Division, Saint Thomas Hospital, Nashville, Tennessee; Department of Pulmonary Medicine, 1st affiliated Hospital of Zhongshan (Sun Yat-sen) University, Guangzhou, Guangdong, China; and Department of Critical Care and Pulmonary Services, Evangelismos Hospital, School of Medicine, University of Athens, Greece

Correspondence and requests for reprints should be addressed to Georgios T. Stathopoulos, M.D., Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T-1218 MCN, Nashville, TN 37232-2650. E-mail: georgios.stathopoulos{at}vanderbilt.edu

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)-B activity in vitro and in vivo, which we used to drive expression of a NF-B–dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-B–dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-B in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-B inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF- levels. These studies indicate that tumor NF-B 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.

Key Words: Lewis lung cancer • lung • adenocarcinoma • bioluminescence • luciferase

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