Abstract 1640: Combined inhibition of EMMPRIN and EGFR abrogates growth and migration of head and neck squamous cell carcinoma cells.

Abstract

Abstract Head and neck cancer squamous cell carcinoma (HNSCC) is the most common malignancy of the upper aerodigestive tract. Despite intense efforts to improve different treatment modalities, mortality rates in advanced cases remain high. A deeper understanding of the HNSCC progression mechanisms is needed to improve survival in patients with HNSCC. The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase, which regulates crucial cellular signaling pathways contributing to tumor progression. EGFR is frequently amplified and overexpressed in several human solid tumors including a high percentage of HNSCCs. Evidence accumulated in several studies has shown that EGFR stimulation induces expression of matrix metalloproteinases (MMPs), which degrade extracellular matrix, and its activation process is critical for tumor development. Recently, extracellular matrix metalloproteinase inducer (EMMPRIN), which is known as CD147 and is a member of the immunoglobulin superfamily, has been reported to be highly expressed in malignant tumors including HNSCC. It has been reported that EGFR expression is associated with EMMPRIN in some solid tumors; however, the relationship of EMMPRIN with EGFR in head and neck cancers is not fully understood. To determine the relationship between EMMPRIN and EGFR in HNSCC, HNSCC cells were stimulated with epidermal growth factor (EGF), a ligand of EGFR. Immunoblotting analysis showed that EMMPRIN expression in HNSCC cells was upregulated by EGF in a dose- and time-dependent manner. In addition, gelatin zymography showed that EGF stimulation-induced cell invasion and MMP-9 expression of HNSCC cells. Interestingly, this increase in invasion and MMP-9 expression were abrogated by downmodulation of EMMPRIN expression using the siRNA technique. Furthermore, to determine the effects of combined EMMPRIN and EGFR targeting in the HNSCC cell line, HNSCC cells were investigated in cell proliferation and migration assays. The effects of combined treatment with the EMMPRIN function blocking antibody and the EGFR inhibitor AG1478 were examined on the proliferation and migration of HNSCC cells. This combined treatment resulted in greater inhibition of HNSCC cell proliferation and migration compared with the individual agents alone. These results suggest that EMMPRIN mediates EGFR-induced invasion and MMP-9 expression in cases where combined targeting of EMMPRIN and EGFR may be an efficacious treatment approach. Citation Format: Shinsuke Suzuki. Combined inhibition of EMMPRIN and EGFR abrogates growth and migration of head and neck squamous cell carcinoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1640. doi:10.1158/1538-7445.AM2013-1640