Balça-Silva, J;
Matias, D;
Do Carmo, AL;
Dubois, L;
Gonçalves, A;
Girão, H;
Canedo, NH;
... Moura-Neto, V; + view all
(2017)
Glioblastoma entities express subtle differences in molecular composition and response to treatment.
Oncology Reports
, 38
pp. 1341-1352.
10.3892/or.2017.5799.
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Abstract
Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines. We evaluated the cell death, cell cycle arrest and cell proliferation, mainly through PKC expression, by flow cytometry and western blot analysis and, ultimately, cell migration capability and f-actin filament disorganization by fluorescence microscopy. We demonstrated that the constitutive activation of p-PKC seems to be one of the main metabolic implicated on GBM malignancy. Despite of its higher resistance, possibly due to the overexpression of P-glycoprotein and stem-like cell markers, GBM11 cells presented a subtle different chemotherapeutic response compared to U87 and U118 cells. The GBM11, U87, U118 cell lines show subtle molecular differences, which clearly indicate the characterization of GBM heterogeneity, one of the main reasons for tumor resistance. The adding of cellular heterogeneity in molecular behaviour constitutes a step closer in the understanding of resistant molecular mechanisms in GBM, and can circumvents the eventual impaired therapy.
| Type: | Article |
|---|---|
| Title: | Glioblastoma entities express subtle differences in molecular composition and response to treatment |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3892/or.2017.5799 |
| Publisher version: | https://doi.org/10.3892/or.2017.5799 |
| Language: | English |
| Additional information: | © Balça-Silva et al. This is an open access article distributed under the terms of Creative Commons Attribution License. |
| Keywords: | Glioblastoma, glioma cancer stem-like cells, cellular heterogeneity, chemotherapeutic resistance, cell motility |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10053155 |
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