Abstract 5192: Platelet derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity

Abstract

Abstract Growth factor-mediated proliferation and self-renewal maintains tissue specific stem cells and is frequently dysregulated in cancers. Platelet-derived growth factor ligands and receptors (PDGFRs) are commonly overexpressed in gliomas and initiate tumors in genetically engineered models. PDGFRα alterations inform intertumoral heterogeneity towards a proneural glioma subgroup. We interrogated the role of PDGFRs in intratumoral heterogeneity with regards to differences in tumor cells. We found that PDGFRα is expressed only in a subset of gliomas while PDGFRβ is more commonly expressed in tumors but largely restricted to self-renewing tumorigenic glioma stem cells (GSCs). Targeting PDGFRβ genetically or with specific inhibitors attenuated GSC self-renewal, survival, tumor growth, and invasion. PDGFRβ targeting was associated with decreased activation of the cancer stem cell signaling node STAT3, and STAT3 activity rescued loss of PDGFRβ expression. These results demonstrate that a growth factor receptor family can differentially function to promote tumor heterogeneity. Our results may explain mixed clinical responses of anti-PDGFR based approaches, and suggest the need for integration of models of cancer as an organ system into development of cancer therapies. 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 5192. doi:1538-7445.AM2012-5192