Development of lung metastases in new animal models of OSCC


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Sabrina Marcazzan1,Ali Dadbin2,Giulia Brachi3,Elvin Blanco2,Elena Maria Varoni1,Giovanni Lodi1,Mauro Ferrari2
1University of Milan,2Houston Methodist Research Institute,3Politecnico di Torino

Abstract

Background

Oral Squamous Cell Carcinoma (OSCC) is the sixth most common cancer worldwide. While the early stages present a positive outcome, the 5 years overall survival of advanced ones is less than 50%, especially when regional or distant metastases occur. In the preclinical setting, few animal models of metastatic OSCC have been developed and the growth of metastases is still poorly understood. Here we report the development of two mouse models of metastatic OSCC by orthotopic and intravenous (IV) injection.

Method

For the orthotopic model, HSC-3 cells expressing luciferase and GFP were injected in the tongue of 5-6 weeks old athymic nude mice. The presence of the primary tumor and lung metastasis was evaluated by in vivo and ex vivo imaging techniques and further confirmed by H&E and human pan-cytokeratin staining. For the IV model, 7-8 weeks old athymic nude mice were injected with tumor cells isolated from HSC-3 lung metastasis of a mouse injected IV.

Results

In the orthotopic model, lung and regional lymph node metastases were present in 40%-80% of the animals by ex vivo imaging 40-50 days after cell injection. Histological analysis of the primary tumors showed infiltration of the deep muscular layer. Histology and IHC confirmed the presence of large lymph node and lung metastases. In the IV model, large lung metastases were present in the 60% of the animals by ex vivo imaging 42 days after cell injection. The presence of lung metastases was further confirmed by histology. No regional lymph node metastases were detected in this model. 

Conclusion

Both regional lymph node and lung metastases were observed in the orthotopic model of OSCC. In the IV model, only lung metastases were present. Both models can be used to investigate the mechanism of metastases in OSCC.