Abstract 561: Tumor-associated fibroblast-induced head and neck squamous cell carcinoma invasion can be abrogated by c-Src and c-Met inhibition

Abstract

Abstract Purpose: Mortality from head and neck squamous cell carcinoma (HNSCC) is usually associated with locoregional invasion of the tumor into vital organs including the airway. There are currently no treatments that abrogate HNSCC tumor invasion. HNSCC tumors are frequently associated with reactive fibroblasts. Our preliminary data demonstrate that stromal fibroblasts in the vicinity of the tumor induce phosphorylation of c-Src and induce HNSCC invasion. We reported that tumor-associated fibroblasts (TAF) secrete HGF that binds to the c-met receptor on HNSCC activating downstream signaling contributing to the invasive phenotype. In addition we have previously reported that c-Src plays an important role in mediating HNSCC invasion. We hypothesize that blocking c-Met and c-Src in HNSCC cells will abrogate TAF induced HNSCC invasion. Experimental design: Inhibition of c-Met and c-Src was achieved by a combination of small molecule inhibitors and dominant negative approaches. The effect of inhibition of c-Met and c-Src on invasion of HNSCC cells was assessed in an in vitro Matrigel coated transwell invasion assay. Results: We demonstrate that inhibition of c-Met or c-Src with inhibitors or using dominant-negative constructs attenuated TAF-stimulated HNSCC invasion. Combined inhibition of c-Met and c-Src resulted in further attenuation of HNSCC cell invasion in vitro.Conclusions: These cumulative results suggest that TAF-induced signaling through c-Met and c-Src contribute to HNSCC invasion and that targeting these pathways may be a novel strategy to prevent tumor invasion and metastasis in HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 561. doi:10.1158/1538-7445.AM2011-561