Abstract LB-518: Amplification and activation of EGFR wild-type mediates invasion of human glioblastoma in vivo

Abstract

Abstract Glioblastoma (GBM) is the most aggressive form of primary brain tumors with a median survival of 15 months. Although angiogenesis is one of the main features of GBMs, non-angiogenic tumor infiltration into brain parenchyma still is the major challenge for therapy. Tumor cells can migrate very far from the main tumor mass and the invasive pattern of tumor subpopulations has not been characterized properly. Epidermal growth factor receptor (EGFR) gene amplification is one of the major mutations of primary GBMs, where multiple copies of the wild-type EGFR gene are present as double minutes. Although studies have proposed a role for EGFR gene amplification in tumor development, the function of EGFR in vivo is not characterized properly mainly due to inefficient tumor models. Here, we report a key role for EGFR wild-type in tumor invasion. In a human GBM xenograft model, we show that tumor cells with EGFR amplification and expression are highly invasive and non-angiogenic. By blocking EGFR activation using Cetuximab and a dominant-negative approach, we show that maintenance of the non-angiogenic, invasive growth pattern is dependent on EGFR function and that downregulation of its activity leads to angiogenic tumor growth. As EGFR amplification and expression is present in 40-60% of GBMs, our results might implicate that activation of EGFR wild-type is one of the major mechanisms of glioblastoma invasion in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-518. doi:1538-7445.AM2012-LB-518