Abstract 5061: Astrocytes promote medulloblastoma tumorigenesis via sonic hedgehog secretion

Abstract

Abstract Tumor development is a complex process that involves interactions between tumor cells and the surrounding cells (the microenvironment). However, in medulloblastoma (MB), the most common malignant pediatric brain tumor, the contribution of the tumor microenvironment in tumorigenesis still remains elusive. Using MB mouse models, we have recently found that astrocytes represent the major component of the MB microenvironment. Astrocytes significantly enhance MB cell proliferation in vitro and genetic ablation of astrocytes dramatically prevents MB cell proliferation and inhibits MB growth in tumor-bearing mice. These results indicate the critical role of astrocytes during MB development. Our studies have further revealed that astrocytes stimulate proliferation of MB cells by secretion of sonic hedgehog (Shh), a mitogen required for neuronal proliferation during normal development. It is well established that Shh triggers canonical hedgehog signaling via activation of the Gli1 transcription factor. Interestingly, astrocyte-derived Shh stimulates MB cell proliferation independent of Gli1 activation, suggesting that astrocytes promote MB tumorigenesis through a novel Shh signaling pathway. Together, our studies shed light on the important function of the tumor microenvironment in MB initiation and progression, and pave the road to develop therapeutic approaches to treat MB by targeting Shh secretion in astrocytes. Note: This abstract was not presented at the meeting. Citation Format: Larra Walling Yuelling, Fang Du, Eric Lee, Renata Muradimova, Peng Li, Zeng-jie Yang. Astrocytes promote medulloblastoma tumorigenesis via sonic hedgehog secretion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5061. doi:10.1158/1538-7445.AM2015-5061