Aldehyde dehydrogenase 1 (ALDH1) has been identified in stem cells from both normal and cancerous tissue. This study aimed to evaluate the potential of ALDH1 as a universal brain tumor initiating cell (BTIC) marker applicable to primary brain tumors and their biological role in maintaining stem cell status. Cells from various primary brain tumors (24 pediatric and 6 adult brain tumors) were stained with Aldefluor and sorted by flow cytometry. We investigated the impact of ALDH1 expression on BTIC characteristics in vitro and on tumorigenic potential in vivo. Primary cultured brain tumor cells showed universal expression of ALDH1, with 0.3 to 28.9% of the cells in various tumors identified as ALDH1+. ALDH1+ cells generate neurospheres with high proliferative potential, express neural stem cell markers (nestin and musashi) and differentiate into multiple nervous system lineages. ALDH1+ cells are phenotypically distinct from CD133+ cells, and they show high expression of induced pluripotent stem cell-related genes. Notably, targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed their self-renewing ability. After three months, ALDH1+ cells gave rise to tumors in 93% of mice whereas ALDH1- cells did not. The characteristic pathology of mice brain tumors from ALDH1+ cells was similar to that of human brain tumors, and these cells are highly proliferative in vivo. Our data suggest that primary brain tumors contain distinct subpopulations of cells that have high expression levels of ALDH1 and BTIC characteristics. ALDH1 might be a potential therapeutic target applicable to primary brain tumors.

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 5343. doi:1538-7445.AM2012-5343