Establishment of an orthotopic C3H mouse model of lung cancer using Lewis lung carcinoma (LLC) cells

Lung cancer continues to be the foremost cause of cancer-related mortality worldwide, characterized by increasing incidence and significant metastatic capability that contributes to unfavorable outcomes. The development of effective therapies is critically dependent on robust preclinical animal models that can accurately mimic the characteristics of the disease. This study describes the establishment and validation of an orthotopic C3H mouse model using the Lewis lung carcinoma (LLC) cell line. C3H mice were used to explore the feasibility of the model in an alternative immunocompetent strain. The model was successfully induced, and subsequent analysis of the tumor microenvironment revealed a significant increase in key pro-inflammatory and pro-angiogenic factors. The study identified significantly increased concentrations of tumor necrosis factor-alpha (TNF-α, 11-fold), vascular endothelial growth factor (VEGF, 1.1-fold), and angiopoietin-2 (Ang-2, 1.2-fold) in the intrapulmonary LLC-induced animals relative to untreated controls. These findings confirm that the model effectively recapitulates the pro-angiogenic and inflammatory conditions essential for tumor growth and metastasis. In conclusion, the orthotopic C3H mouse model induced with the LLC cell line provides a platform for understanding disease mechanisms and evaluating novel therapeutic interventions targeting angiogenesis and inflammation. While the model is effective, researchers must consider that potential variability in tumor growth and metastasis may arise from factors such as genetic drift in the cell line and individual host immune responses.