glioblastoma formation from cell population depleted of prominin1-expressing cells胶质母细胞瘤细胞群耗尽prominin1-expressing细胞形成.pdfVIP

Glioblastoma Formation from Cell Population Depleted of Prominin1-Expressing Cells 1,2 1 2 1 Kenji Nishide , Yuka Nakatani , Hiroshi Kiyonari , Toru Kondo * 1 Laboratory for Cell Lineage Modulation, Center for Developmental Biology, RIKEN, Kobe, Japan, 2 Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology, RIKEN, Kobe, Japan, 3 Department of Biology, Graduate School of Science, Kobe University, Kobe, Japan Abstract Prominin1 (Prom1, also known as CD133 in human) has been widely used as a marker for cancer stem cells (CSCs), which self-renew and are tumorigenic, in malignant tumors including glioblastoma multiforme (GBM). However, there is other evidence showing that Prom1-negative cancer cells also form tumors in vivo. Thus it remains controversial whether Prom1 is a bona fide marker for CSCs. To verify if Prom1-expressing cells are essential for tumorigenesis, we established a mouse line, whose Prom1-expressing cells can be eliminated conditionally by a Cre-inducible DTA gene on the Prom1 locus together with a tamoxifen-inducible CreERTM, and generated glioma-initiating cells (GICs-LD) by overexpressing both the SV40 Large T antigen and an oncogenic H-RasL61 in neural stem cells of the mouse line. We show here that the tamoxifen-treated GICs- LD (GICs-DTA) form tumor-spheres in culture and transplantable GBM in vivo. Thus, our studies demonstrate that Prom1- expressing cells are dispensable for gliomagenesis in this mouse model. Citation: Nishide K, Nakatani Y, Kiyonari H, Kondo T (2009) Glioblastoma Formation from Cell Population Depleted of Prominin1-Expressing Cells. PLoS ONE 4(8): e6869. doi:10.1371/journal.pone.0006869 Editor: Pedro R. Lowenstein, Cedars-Sinai Medical Center and University of California Los Angeles, United Stat