Abstract 1484: CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor cells

Abstract

Abstract Glioblastoma multiforme (GBM) is the most aggressive and lethal brain tumor that occurs both in children and adults. Diffuse invasion into normal brain tissue is one of the important biologic features that make GBM refractory to conventional therapies. While existing studies on GBM invasion are primarily conducted using tumor core tissues from surgical resections, it is unclear whether unresectable, infiltrative GBM cells would be more informative for studying their invasive nature compared to those in the resected tumor cores. More importantly, little is known if and which cancer stem cell populations are driving glioma invasion. To address these fundamental issues, we utilized our panel of 7 (6 pediatric and 1 adult) patient tumor-derived orthotopic xenograft mouse models of GBM to isolate invasive GBM cells (infiltrating normal mouse brain parenchyma) and tumor core GBM cells and directly compared their biological differences. Our result showed that the invasive cells have stronger neurosphere forming efficiency in vitro in a serial dilution assay and increased tumorigenic capacity after in vivo transplantation (particularly at 100 cells/mouse) compared to the tumor core cells. A screening of putative cancer stem cell markers (CD133, CD15, CD24/CD44, CD57 and CD117) showed that invasive GBM cells are enriched (>2 folds) with CD57+ cells compared to the tumor core cells, and these infiltrating cells were predominantly CD57+/CD133-. Even the CD133+ cells were frequently dual-positive with CD57 (CD33+CD57+), not only in the xenograft tumors but also in a separate set of patient GBM samples. Mechanistically, we found that CD57+ cells expressed high levels of self-renewal genes and tend to stay in G0/G1 phases. In conclusion, we showed that invasive GBM cells are biologically deferent from the matched tumor core cells and identified CD57 as a novel stem cell marker that is associated with GBM infiltration. Our findings suggest that new anti-invasion therapies should target CD57+ cells in addition to CD133+ cells in GBM. Citation Format: Lin Qi, Yu-lun Huang, Mari Kogiso, Hua Mao, Patricia Baxter, Jack MF Su, Laszlo Perlaky, Ching C. Lau, Murali Chintagumpala, Xiao-Nan Li. CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor cells. [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 1484. doi:10.1158/1538-7445.AM2014-1484