BioProject

Human papillomavirus (HPV) is currently the most identifiable cause of head and neck squamous cell carcinoma (HNSCC) accounting for approximately 25% of these cases. More...

Human papillomavirus (HPV) is currently the most identifiable cause of head and neck squamous cell carcinoma (HNSCC) accounting for approximately 25% of these cases. HPV+ cancer incidence is on the rise with metastatic disease accounting for nearly all HPV+ HNSCC related deaths. Thus, developing a relevant in vivo pre-clinical model for these invasive cancers is necessary for testing new disease therapeutics and improving survival. To this end, we characterize a novel metastatic HPV+ murine model of HNSCC. Individual metastatic clonal cell lines were isolated from an animal with late pulmonary metastasis that developed recurrent disease after standard of care cisplatin-radiation therapy. Similar to the parental cells, all metastatic cell lines retain expression of HPV16 E6 and E7 oncogenes and degrade P53. While the in vitro growth rates of these metastatic clones are slower than the parental tumor line their in vivo growth is greatly enhanced. Moreover, resistance to standard therapies (cisplatin and radiation) is dramatically increased in 3 of the 4 clones in vivo. Lymphatic and/or lung metastasis occurs 100% of the time in 2 of the clonal lines while it is nearly undetectable in the parental line. In addition, expression and protein array analyses were completed to investigate the mechanisms driving these phenotypic changes. This model not only provides an economical and rapid screening system in which to develop and test improved therapeutic regimens but may also provide mechanistic insights into tumor metastasis. Overall design: Comparison of four individual MLM metastatic lines to the parental mEERL cells. These data demonstrate heterogeneity found in metastastatic cells lines compared to the parental tumor cell line Less...