Establishment of a malignant pleural effusion mouse model with lewis lung carcinoma cell lines expressing enhanced green fluorescent protein

Background and objective: Malignant pleural effusion (MPE) is a poor prognostic factor in patients with advanced lung cancer. The aim of this study is to establish a mouse model of MPE using Lewis lung carcinoma (LLC) cell lines expressing enhanced green fluorescent protein (EGFP). Methods: The mouse model was created by injecting LLC-EGFP cells directly into the pleural cavity of nude mice under the guidance of stereomicroscope and then mice were sacrificed periodically. The dynamic growth and metastasis of tumor cells were screened using in vivo fluorescence imaging. The remaining mice were subjected to transverse computed tomography (CT) periodically to analyze the rate of MPE formation. The survival rate and tumor metastasis were also observed after modeling. Pleural fluid was gently aspirated using a 1 mL syringe and its volume was measured. When two or more mice bore MPE at the same time, we calculated the average volume. The correlation of MPE with the integrated optical density (IOD) were analyzed. Results: Four days after the inoculation of LLC-EGFP cells, green fluorescence was observed by opening the chest wall. The tumor formation rate was 100%, and the IOD gradually increased after inoculation. The metastatic foci were mediastinal, contralateral pleural and pericardial. The metastasis rates were 87%, 73%, and 20%, respectively. CT imagings revealed that the rates of MPE formation on days 7, 14 and 21 were 13%, 46%, and 53%. The mean survival time of nude mice was 28.8 days. The average MPE volume increased obviously on day 10 and peaked on day 16 with a value of 0.5 mL. The MPE volume and IOD were significantly correlated (r=0.91, P<0.0001). Conclusions: This study was the first to establish a mouse model of MPE by injecting LLC-EGFP into the pleural cavity under the guidance of a stereomicroscope. The model can enable dynamic observations of the biological behavior of tumor cells in the pleural cavity. It might be helpful for basic research on advanced lung cancer as well as anti-tumor drug development.