Abstract 530: The role of EGFR in c-fos-dependent osteosarcoma formation

Abstract

Abstract The Epidermal Growth Factor Receptor (EGFR) is overexpressed or mutated in human carcinomas and glioblastomas, which are tumors of epithelial and glial origin, respectively. Some publications indicated that EGFR overexpression could occur in human osteosarcomas (OS). Using EGFR knockout mice (Egfr-/-), we have recently shown that EGFR plays a role in bone development and osteoblast function, raising the possibility that EGFR is also involved in OS formation. Here we show that Egfrf/f Runx2-Cre mice (EgfrΔOb), lacking the EGFR in osteo-chondroprogenitor cells, develop an increased zone of hypertrophic chondrocytes in long bones and decreased bone formation. When bred to c-fos transgenic mice (H2-c-fosLTR) that develop osteosarcomas with 100% penetrance, EgfrΔOb mice show reduced tumor incidence and burden. At the molecular level, tumors from EgfrΔOb mice exhibit decreased expression levels of c-Fos and Cyclin D1. In vitro experiments in primary bone tumor cells further show that EGFR inhibition leads to reduced proliferation and increased apoptosis. Importantly, Egfr and c-Fos also play an important role in human OS, as co-expression of both proteins in tumor sections correlated with significantly reduced survival in patients suffering from primary OS. Taken together our data suggest an essential role of EGFR signaling during both development and progression of c-Fos-dependent OS and newly identified molecular targets currently under investigation will be presented. Citation Format: Markus Linder, Elisabeth Glitzner, Sriram Srivatsa, Parastoo Shahrouzi, Latifa Bakiri, Monika Dumanic, Markus Mitterhauser, Erwin F. Wagner, Maria Sibilia. The role of EGFR in c-fos-dependent osteosarcoma formation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 530. doi:10.1158/1538-7445.AM2017-530