Abstract 66: Inhibition of glioma cell proliferation and tumor development by Sox21

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Sox2 and Sox21 are two transcription factors important for the developing, as well as the adult, CNS, and they are often co-expressed. Sox2 is an embryonic stem cell marker, whereas ectopic forced expression of Sox21 has been shown to induce differentiation in embryonic stem cells. Further, Sox2 is important for maintenance of neural stem cells whereas Sox21 is important for neurogenesis. These two transcriptionfactors are thus in opposite relation to each other and it is believed that a proper balance between them is needed to regulate target genes. Sox2 is highly expressed in brain tumors and up to 97% of GBM samples express Sox2. While the expression of Sox2 has been shown in GBM, in primary glioma cells and established glioma cell lines, less is known about Sox21 in glioma. We have previously shown that Sox2 and Sox21 are co-expressed in adult and childhood brain tumors and are in a functional relationship in glioma cells. Sox2 keeps glioma cells in a proliferative state whereas over expression of Sox21 reduces Sox2 expression and decreases cell proliferation with an increased tendency of apoptosis and differentiation of the glioma cells. We have now further elucidated this effect in vivo by injecting established inducible-Sox21 glioma cell lines subcutaneously into the flank and orthotopically into the brain of SCID mice. Regardless of the injection site, increased Sox21 expression in these tumors reduces tumor growth. The tumors from treated mice were significantly smaller in size and there is a significant increase in survival time. This effect was dependent on the time of Sox21 induction, where an earlier turn on gives even smaller tumors. Total depletion of Sox2 was not achieved despite forced Sox21 expression. Further we show that Sox2 deficiency leads to an inability to form tumors. With its dual effect, the ability to decrease Sox2 expression and the ability to aberrantly differentiate tumor cells, Sox21 becomes a very important factor for future research around therapeutic possibilities in GBM. 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 66. doi:1538-7445.AM2012-66