DEVELOPMENT OF MOUSE MODELS OF ORAL SQUAMOUS CELL CARCINOMA (OSCC) METASTASIS FOR THE EVALUATION OF EMERGING ANTI-METASTATIC NANOMEDICINE DRUGS

Oral Squamous Cell Carcinoma (OSCC) is included in the Head and Neck Squamous Cell Carcinoma (HNSCC) group, which is the sixth most common cancer diagnosed worldwide. While the locoregional control has been increased thanks to the combination therapy, the incidence of distant metastasis is increasing. Nanomedicine therapies have been clinically approved for the treatment of several types of cancers and were used in few clinical trials on HNSCC patients. However, the efficacy of nanomedicine therapies was limited, especially for the treatment of metastatic OSCC. In the preclinical setting, more advanced nanomedicine platforms have been developed against metastatic cancers. One of this platform, iNPG-pDox, obtained promising results against lung metastasis in a preclinical model of breast cancer. The lungs are the most common site of distant metastasis reported in OSCC and there is an unmet need for novel therapies targeting distant metastasis. The aim of the present work was to establish two preclinical models of OSCC lung metastasis by orthotopic and tail vein injection of OSCC cells and to perform preliminary in vitro evaluations of pDox nanoparticles in two cell lines of metastatic OSCC (HSC-3 and HSC-3 M1, isolated from HSC- 3 lung metastases). In vitro, pDox nanoparticles were able to effectively kill both HSC-3 and HSC-3 M1 cells, without any significant difference between the two cell lines. In vivo, lung metastases of OSCC were observed in both preclinical models. In particular, the orthotopic model also developed regional lymph node metastases, characteristic of metastatic growth observed in OSCC patients. The other model obtained by tail vein injection presented only lung metastases. Therefore, orthotopic models should be preferred to non-orthotopic models for the preclinical evaluation of anti-metastatic nanomedicine therapies such as iNPG-pDox in OSCC. Moreover, such preclinical model of OSCC lung metastasis may be used to investigate the molecular mechanisms of OSCC regional and distant metastasis, which are still poorly understood.