Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation

Abstract

Glioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis.

Golgi Phosphoprotein 3 Regulates the Physical Association of Glycolipid Glycosyltransferases

“…To study the involvement of GOLPH3 in the metabolism of glycolipids, we took advantage of the T98G cell line, a broadly used model of glioblastoma multiforme [ 35 , 36 ]. In addition, T98G cells show high levels of GOLPH3 in respect to control human astrocytes from primary culture, indicating that this cell is useful for studying the functional effects of lowering the expression of GOLPH3 [ 37 , 38 ].…”

Temozolomide-Acquired Resistance Is Associated with Modulation of the Integrin Repertoire in Glioblastoma, Impact of α5β1 Integrin

“…One of the most affected pathways was, in both cases, extracellular matrix organization, including integrin expression level modifications. Interestingly, profound changes in ECM–receptor interactions were also noted in the response of the glioma to ionizing radiation [ 57 ]. The heatmap of integrins ( Figure 4 ) revealed particular sets of integrins overexpressed in each cell line, suggesting that anti-integrin therapeutic options have to be considered in a timely manner during therapies.…”

Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

“…Further, using SELEX technology on T98G target cells and SVGp12 off-target cells, Wu et al selected two aptamers, WYZ-41a and WYZ-50a, able to bind to T98G but not to either U87 and U251 GBM cell lines [91] consistently, with major differences at the cell surface among them [92]. The aptamers were stable for 2 h and retained their binding capability in cerebral spinal fluid, thus indicating a great potential in using these aptamers for biomedical applications.…”