Induced Differentiation Suppresses The Stem Cell Porperties And Tumorigenesis Of Stem-like Glioma Cells

Objective Use ATRA to induce stem-like glioma cells to differentiate and compare stem-like cells properties and biologic characteristics between stem-like glioma cells, including C6 cell lines, primary glioma cells and their differentiated cells.Methods Glioma cells were cultured with neurosphere-formation assay in serum-free supplemented medium. Stem-like glioma cells (SLGC) were differentiated with all-trans retinoic acid(ATRA)-containing medium. Growth characteristics, including morphological differences, capacity of self-renewal, were detected contrastively through neurosphere formation assay. Expressions of stem cell and differentiated cell markers were determined by reverse transcription polymerase chain reaction (RT-PCR), Western Blotting and Flow Cytometry(FCM). SLGC and differentiated cells were implanted stereotactically and intracranially into the Balb/c nude mice to contrast the capability of tumor initiation and the tumor models were detected by hematoxylin and eosin (HE) staining. All data analyses were performed with the SPSS software, version 17.0.Results Our data suggest that in vitro differentiation of SLGCs with ATRA induces the growth characteristics changes of glioma cells ,down-regulation of CD133 and Nestin expression and up-regulation of GFAP. In vivo mouse model, differentiated cells inoculated mice have better survival outcome. Conclusions1.ATRA can induce the differentiation of SLGCs.2.The tumorigenicity of stem-like glioma cells is reduced after ATRA differentiation.3.Differentiation treatment (ATRA) targeted the stem-like cell population is a candidate for adjuvant therapy against malignant gliomas.