Object: Glioblastoma stem-like cells (GSCs) exhibit stem-like properties, are highly efficient at forming tumor xenografts, and are resistant to many current therapies. Current molecular identifiers of GSCs are scarce and controversial. The authors describe differential cell-surface gene expression profiling to identify GSC-specific markers.
Methods: Independent human GSC lines were isolated and maintained in standard neural stem cell (NSC) media and were validated for self-renewal, multipotent differentiation, and tumor initiation properties. Candidate upregulated GSCspecific plasma membrane markers were identified through differential Affymetrix U133 Plus 2.0 Array gene expression profiling of GSCs, human NSCs (hNSCs), normal brain tissue, and primary/recurrent glioblastoma multiforme samples. Results were validated by using comparative quantitative reverse transcription polymerase chain reaction and Western blot analysis of GSCs, hNSCs, normal human astrocytes, U87 glioma cell line, and patient-matched serum-cultured glioblastoma multiforme samples.
Results: A candidate GSC-specific signature of 19 upregulated known and novel plasma membrane-associated genes was identified. Preferential upregulation of these plasma membrane-linked genes was validated by quantitative polymerase chain reaction. Cadherin-19 (CDH19) protein expression was enhanced in minimally infiltrative GSC lines.
Conclusions: Gene expression profiling of GSCs has shown CDH19 to be an exciting new target for drug development and study of GBM tumorigenesis.
Keywords: ACTB = β-actin; CDH = cadherin; CDH19; CNP = 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase; GBM = glioblastoma multiforme; GPC3 = glypican-3; GPR17 = G protein–coupled receptor 17; GSC = glioblastoma stem-like cell; HLA = human leukocyte antigen; MCPIP = monocyte chemotactic protein 1–induced protein; MHC = major histocompatibility complex; NCBI GEO = National Center for Biotechnology Information Gene Expression Omnibus; NCI REMBRANDT = National Cancer Institute Repository of Molecular Brain Neoplasia Database; NHA = normal human astrocyte; OPC = oligodendrocyte progenitor cell; cadherin-19; gene expression profiling; glioblastoma multiforme; glioblastoma stem-like cells; hNSC = human neural stem cell; oncology; qRT-PCR = quantitative reverse transcription polymerase chain reaction.