Nuclear factor-kappaB affects tumor progression in a mouse model of malignant pleural effusion.
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.
Stathopoulos
Georgios T
GT
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, T-1218 MCN, Nashville, TN 37232-2650, USA. georgios.stathopoulos@vanderbilt.edu
Zhu
Zhiwen
Z
Everhart
M Brett
MB
Kalomenidis
Ioannis
I
Lawson
William E
WE
Bilaceroglu
Semra
S
Peterson
Todd E
TE
Mitchell
Daphne
D
Yull
Fiona E
FE
Light
Richard W
RW
Blackwell
Timothy S
TS
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D018827:Carcinoma, Lewis Lung; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D015552:Injections, Intralesional; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000378:metabolism* / Q000473:pathology*; D010997:Pleural Neoplasms / Q000473:pathology; D011247:Pregnancy
C103558:Ccl12 protein, rat; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D018945:Monocyte Chemoattractant Proteins; D016328:NF-kappa B; D049452:Green Fluorescent Proteins; D007770:L-Lactate Dehydrogenase