Abstract A09: Effects of Podocalyxin on neural stem/progenitor cells

Abstract

Abstract Podocalyxin (PODXL) is a highly glycosylated and sialylated protein found mainly on podocytes and up-regulated in various types of tumors. Known to be a marker of hematopoietic progenitors and pluripotent stem cells, PODXL is also increasingly considered a marker of malignancy in several aggressive tumor types. Though the exact role of PODXL in tumors is not yet established, it has increasingly been shown in vitro to be involved in cell migration and invasion. We found Podxl to be highly expressed in murine tumorigenic neural stem/progenitor cells. To investigate effects of elevated Podxl levels in neural stem/progenitor cells (NSPs), Podxl or an empty control construct were over-expressed in these cells. Podxl-overexpressing NSPs did not form brain tumors upon intracranial transplantations, indicating that high levels of this gene alone are not sufficient for tumorigenesis. In vitro studies however revealed how Podxl might contribute to the development and /or maintenance of tumors. Podxl overexpression had a positive effect on cell number, sphere formation and cell viability. To find out how Podxl exerts its pro-survival effects, the proteome of Podxl-overexpressing and empty control NSPs was analysed by mass spectrometry. These experiments revealed an up-regulation of Annexin A2, a calcium-regulated phospholipid binding protein interacting with the cytoskeleton and extracellular matrix. In addition to elevated Annexin A2 protein levels, we also found increased transcript levels indicating that PODXL stimulates expression of the Annexin A2 gene. NSPs lacking Annexin A2 and overexpressing Podxl are less viable than wild type Podxl-overexpressing NSPs, suggesting that PODXL-mediated pro-survival effects can at least in part be explained by increased Annexin A2 levels. We are now investigating how Podxl and Annexin A2 mechanistically interact to enhance cell viability Citation Format: Isabelle V. Leefa Chong San, Gaelle Prost, Ulrike Nuber. Effects of Podocalyxin on neural stem/progenitor cells. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A09.