This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Koppikar, P. Articles by Grandis, J. R. PubMed PubMed Citation Articles by Koppikar, P. Articles by Grandis, J. R.

Combined Inhibition of c-Src and Epidermal Growth Factor Receptor Abrogates Growth and Invasion of Head and Neck Squamous Cell Carcinoma

Authors' Affiliations: Departments of ¹ Otolaryngology, ² Pharmacology, and ³ Pathology, University of Pittsburgh School of Medicine and ⁴ University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; and ⁵ Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Requests for reprints: Jennifer R. Grandis, 200 Lothrop Street, Suite 500, Pittsburgh, PA 15213. Phone: 412-647-5280; Fax: 412-383-5409; E-mail: jgrandis{at}pitt.edu.

Purpose: Increased expression and/or activation of epidermal growth factor receptor (EGFR) is associated with tumor progression and poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC). Src family kinases, including c-Src, mediate a variety of intracellular or extracellular signals that contribute to tumor formation and progression. This study was undertaken to elucidate the role of c-Src in the growth and invasion of HNSCC and to determine the effects of combined targeting of EGFR and Src kinases in HNSCC cell lines.

Experimental Design: HNSCC cells were engineered to stably express a dominant-active form of c-Src and investigated in cell growth and invasion assays. The biochemical effects of combined treatment with the Src inhibitor AZD0530, a potent, orally active Src inhibitor with Bcr/Abl activity, and the EGFR kinase inhibitor gefitinib were examined, as well as the consequences of dual Src/EGFR targeting on the growth and invasion of a panel of HNSCC cell lines.

Results: HNSCC cells expressing dominant-active c-Src showed increased growth and invasion compared with vector-transfected controls. Combined treatment with AZD0530 and gefitinib resulted in greater inhibition of HNSCC cell growth and invasion compared with either agent alone.

Conclusions: These results suggest that increased expression and activation of c-Src promotes HNSCC progression where combined targeting of EGFR and c-Src may be an efficacious treatment approach.