Abstract 1826: Characterization of HPV-positive head and neck cancer cell lines as preclinical models for targeted therapy

Abstract

Abstract Background:Head and neck squamous cell carcinoma (HNSCC) is the 6th most frequently diagnosed non-skin cancer in the world. Risk factors associated with HNSCC include smoking, alcohol use and human papillomavirus (HPV) infection. With the decline in tobacco use, there has been an increase in the incidence of HPV-associated head and neck cancers. Our increased understanding of the mutational landscape demonstrates that HPV-positive and HPV-negative HNSCC are molecularly distinct. Additionally, patients with HPV-positive tumors respond better to therapy and have better prognosis overall. However, there are no targeted therapies for HPV+ HNSCC. Human cell lines can serve as preclinical models for studying cancer progression and identifying possible therapeutic targets. Our aim was to determine if HNSCC tumors and cell lines derived from head and neck tumors display similar proteomic profiles. Methods: Reverse phase protein array (RPPA) analysis was performed on 66 HNSCC cell lines. The HPV-status of these cell lines was determined by quantitative and reverse transcriptase polymerase chain reaction (PCR). Results: Real-time PCR analysis confirmed that 9 of the 66 cell lines were HPV-positive. Differential expression of 156 proteins was analyzed and proteomic pathway scores were determined by t-test in HPV-positive and HPV-negative HNSCC cell lines. We identified significant proteomic differences between HPV-positive and negative HNSCC cell lines. As observed in HPV-positive head and neck tumors, the clinical biomarker p16 was overexpressed in HPV-positive cell lines (p-value <0.0001). Furthermore, the expression of other cell cycle proteins p21 (p-value <0.0001) is lower in HPV-positive cell lines while cyclin E1 (p-value <0.03) and pRb (p-value <0.0001) are higher in HPV-positive cell lines. Similar to RPPA profiles of HNSCC tumors, HPV-positive cell lines show less epithelial to mesenchymal transition as indicated by lower levels of fibronectin and N-cadherin. When compared to HNSCC tumors, we also observed dysregulated expression of receptor tyrosine kinases such as epidermal growth factor receptor (EGFR). In comparison to HNSCC tumors, cell lines share similar trends in proteomic profiles. Conclusion: Our findings suggest that HNSCC cell lines are suitable preclinical models for the discovery of pathways activated in HPV-positive HNSCC and identification of possible targets for new therapeutic strategies. Citation Format: Nene N. Kalu, Tuhina Mazumdar, Lixia Diao, Patrick Kwok Shing Ng, Jing Wang, Jeffery Myers, Faye M. Johnson, Lauren Averett Byers. Characterization of HPV-positive head and neck cancer cell lines as preclinical models for targeted therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1826. doi:10.1158/1538-7445.AM2015-1826