Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

• DOI: 10.1158/1078-0432.ccr-09-0695
• Publication Date: 2009-10-28T01:10:20Z
• Authors: Aurélie Ernst; Stefanie Hofmann; Rezvan Ahmadi; Natalia Becker; Andrey Korshunov; Felix Engel; Christian Hartmann; Jörg Felsberg; Michael Sabel; Heike Peterziel; Moritz Durchdewald; Jochen Hess; Sebastian Barbus; Benito Campos; Anna Starzinski-P...; Andreas Unterberg; Guido Reifenberger; Peter Lichter; Christel Herold-M...; Bernhard Radlwimmer
• Keywords: Spheroid; Tissue microarray

Glioblastoma spheroid cultures are enriched in tumor stem-like cells and therefore may be more representative of the respective primary tumors than conventional monolayer cultures. We exploited glioma culture model to find novel tumor-relevant genes.We carried out array-based comparative genomic hybridization derived from 20 glioblastomas. Microarray-based gene expression analysis was applied determine genes with differential compared normal brain tissue nonneoplastic spheroids The protein levels three candidates were determined by immunohistochemistry on microarrays correlated clinical outcome. Functional PDPN done.Genomic changes closely resembled those detected corresponding patients. In contrast, serum-grown established same patients did not match well tumors. glioblastoma identified a set candidate being upregulated or downregulated relative brain. Quantitative real-time PCR analyses 8 selected samples validated microarray findings. Immunohistochemistry revealed that AJAP1, EMP3, significantly associated overall survival astrocytic Invasive capacity RhoA activity decreased PDPN-silenced spheroids.We likely play role pathogenesis implicate as molecular markers outcome