Comparison of GFP-Expressing Imageable Mouse Models of Human Esophageal Squamous Cell Carcinoma Established in Various Anatomical Sites

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. Mouse models of this disease could be used for discovery of more effective therapy for ESCC. The green fluorescent protein (GFP)-expressing human esophageal cancer EC1 cell line was established with a lentiviral expression system. Subsequently, nude mice were injected subcutaneously, intracardiac or intravenously, or orthotopically implanted with EC1-GFP cells. Tumor growth and metastasis were examined by fluorescence in vivo imaging or by open fluorescence imaging after autopsy. Four different mouse xenograft models of ESCC expressing GFP were established. In the subcutaneous model, primary tumor growth was monitored in real-time by whole-body fluorescence imaging. No metastasis was observed in the subcutaneous or surgical orthotopic implantation model. By 55 days after implantation, all mice had developed orthotopic esophageal cancer, but without detectable metastasis. In contrast, experimental metastasis occurred in the intracardiac and intravenous models. In the intravenous injection model, the lung was the sole organ of experimental metastasis. In the intracardiac model, extensive experimental metastases occurred in the bone, brain and lung. The mouse xenograft models of ESCC developed in the present study can provide a means of discovering more effective therapy of this recalcitrant type of cancer.