The Role of DRR in Glioma Invasion and Stemness
Author | : Mai Sater |
Publisher | : |
Total Pages | : |
Release | : 2017 |
Genre | : |
ISBN | : |
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"Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor in adults, and has a poor prognosis. Treatment failure in GBM is due to the rapid invasion of cancer cells into the normal brain, and presence of GBM stem cells (GSCs) which are a rare subpopulation of cells within the tumor that contribute to GBM recurrences. GSCs are characterized by their self-renewal capacity and resistance to adjuvant therapy. Previous work in the Petrecca lab has identified and characterized Downregulated in Renal Carcinoma (DRR) as a novel promoter of brain cancer invasion by modulating the cell motility machinery. As a clinically relevant model for glioma invasion, we have implanted human GSCs into the corpus callosum of mice, which these cells readily invade. We observed that DRR-silenced invading GSCs remain confined to the peri-tumoral region compared to DRR-expressing GSCs, which showed extensive invasion across the corpus callosum. In the second part, we show that DRR is highly expressed in all 8 GSCs tested, and positively regulates the expression of key transcription factors that control GSCs self-renewal including Sox2, Olig2, POU3F2 and SALL2. Furthermore, elimination of DRR expression in GSCs increased their sensitivity to temozolomide treatment in vitro, and reduced tumor size in a xenograft GSC mouse model. Collectively, our data show that targeting DRR expression hinders GSCs invasion and reduces their stem cell properties, making DRR a promising target for brain cancer therapy." --