Abstract 2077: Snail modulates stemness properties in hypoxic Glioblastoma

Abstract

Abstract Introduction: Glioblastoma (GBM) is the most aggressive form of glioma characterized by hypoxic regions with surrounding areas of necrosis. Hypoxia is responsible for inducing cancer invasiveness via epithelial-mesenchymal transition (EMT), thereby promoting tumor aggressiveness and therapeutic resistance. HIF-1α is known to upregulate Snail in various cancers. Snail over expression correlates with cancer stem cell-like properties in cancers. The association of EMT and stemness properties plays a vital role in tumors progression and might helps in therapeutic targeting. We have, therefore, investigated the correlation of EMT and Stem cell markers in hypoxic GBM. Method: mRNA expression of 5 EMT, 3 stemness and 5 hypoxia markers were analyzed in the 31 GBM samples and U373MG glioma cell line maintained under normoxia (20% O2) and severe hypoxia (0.2% O2) conditions for 24, 48 and 72 hrs. Correlation and cluster analysis were applied using SPSS 11.5, Cluster 3.0 software etc and R-software. Result: In tumors, spearman correlation was found to be significant (p≤0.05) between EMT markers and Hypoxia markers. Of all EMT markers, Snail correlated significantly with the maximum hypoxia markers, including HIF-1α. In addition, Snail was significantly correlated with Stem cell markers SOX2 (p<0.01) and Nestin (p<0.05). Gene Cluster analysis in 31 GBM arranged in decreasing order of Snail expression showed significant upregulation of SOX2 and Nestin in the high Snail expressing tertile. This correlation of gene expression in tumors was validated by in-vitro expression analysis of the molecules in U373MG cells, where we assessed significant increase in the expression of hypoxia markers (HIF-1α, VEGF and CA9), EMT (Snail and LOX) and SC markers (SOX2 and OCT4) were significantly increased under severe hypoxic conditions. Interpretation & conclusions: Our finding for the first time suggests the role of Snail in provoking stemness of cancer cells in hypoxic GBM, thereby promoting aggressiveness of GBM. Note: This abstract was not presented at the meeting. Citation Format: Chitrangda srivastava, Khushboo Irshad, Arpit Sahu, Parthaprasad Chattopadhyay, Chitra Sarkar, Deepak kumar Gupta, Subrata Sinha, Kunzang Chosdol. Snail modulates stemness properties in hypoxic Glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2077. doi:10.1158/1538-7445.AM2014-2077