Nuclear factor-kappaB affects tumor progression in a mouse model of malignant pleural effusion.

Stathopoulos GT, Zhu Z, Everhart MB, Kalomenidis I, Lawson WE, Bilaceroglu S, Peterson TE, Mitchell D, Yull FE, Light RW, Blackwell TS
Am J Respir Cell Mol Biol. 2006 34 (2): 142-50

PMID: 16210694 · PMCID: PMC2644178 · DOI:10.1165/rcmb.2005-0130OC

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.

MeSH Terms (18)

Animals Body Fluids Carcinoma, Lewis Lung Chemokine CCL2 Disease Models, Animal Female Green Fluorescent Proteins I-kappa B Proteins Injections, Intralesional L-Lactate Dehydrogenase Male Mice Mice, Inbred C57BL Monocyte Chemoattractant Proteins NF-kappa B Pleural Effusion, Malignant Pleural Neoplasms Pregnancy

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