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| Status |
Public on Sep 11, 2012 |
| Title |
Identification of novel genes associated with human glioblastoma (GBM) tumor-initiating cells (TICs) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Most patients affected by Glioblastoma multiforme (GBM) experience a recurrence of the disease because of the spreading of tumor-initiating cells (TICs) beyond surgical boundary. Unveiling and targeting molecular mechanisms causing this process is a logic goal to impair GBM killing ability.
In an orthotopic xenograph model, we have noticed that GBM TICs isolated from several patients may fall into two classes of invasive behavior: nodular or diffuse. In order to identify genes responsible for the diffusive type of invasion, we have compared by genome expression analysis, cultured GBM TICs belonging to the two classes. This analysis allowed us to identify a small group of regulated genes in the diffusive type of GBM TICs. The gene ontology process of cell adhesion and the localization of the gene product functions to the plasmamembrane resulted significantly associated to this gene set. Real time RT-PCR and immunofluorescence analyses performed for a selected subgroup of regulated genes/gene products confirmed the results obtained by the expression analysis. Some of the genes that we found upregulated in our screening were already proven to be involved in Glioma cell invasion supporting our study. However, we have also identified genes that were not previously implicated in this process. To assess whether these are required to sustain TICs GBM invasion, we silenced a subset of them and evaluated in Boyden chamber the invasive ability of the cells.
Our study provides novel target genes to be evaluated for the inhibition of GBM diffusion within the SNC.
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| Overall design |
As we observed that GBM TICs may fall into two classes of “in vivo” invasive behavior in mouse orthotopic transplantation: expansive or highly diffusive, resulting in the host’s white and gray matters substitution, we decided to identify genes associated with the latter phenotype by microarray analysis. Three replicates of each class were analyzed.
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| Contributor(s) |
Monticone M, Daga A, Candiani S, Biollo E, Fabiano A, Romeo F, Melotti A, Corte G, Castagnola P |
| Citation(s) |
22901239 |
| |
| Submission date |
Jun 25, 2009 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Massimiliano Monticone |
| E-mail(s) |
massimiliano.monticone@istge.it
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| Organization name |
IRCCS AOU San Martino – IST, Genova
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| Lab |
S.S. Biofisica e Citometria
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| Street address |
Largo R. Benzi, 10
|
| City |
Genova (GE) |
| ZIP/Postal code |
16132 |
| Country |
Italy |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA117521 |
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