http://www.cnr.it/ontology/cnr/individuo/prodotto/ID286519
PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment (Articolo in rivista)
- Type
- Label
- PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment (Articolo in rivista) (literal)
- Anno
- 2014-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1186/1476-4598-13-247 (literal)
- Alternative label
1Carlo Cenciarelli, 2Hany ES Marei, 1Manuela Zonfrillo, 1Pasquale Pierimarchi, 3Emanuela Paldino, 3Patrizia Casalbore, 3Armando Felsani, 4Angelo Luigi Vescovi, 5Giulio Maira, and 5Annunziato Mangiola (2014)
PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment
in Molecular cancer
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- 1Carlo Cenciarelli, 2Hany ES Marei, 1Manuela Zonfrillo, 1Pasquale Pierimarchi, 3Emanuela Paldino, 3Patrizia Casalbore, 3Armando Felsani, 4Angelo Luigi Vescovi, 5Giulio Maira, and 5Annunziato Mangiola (literal)
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- 1Institute of Translational Pharmacology-CNR, Roma-Italy,
2Department of Cytology and Histology, Mansoura University, Mansoura-Egypt,
3Institute of Cell Biology and Neurobiology-Roma-Italy,
4Department of Biotechnologies and Biosciences, University of Milan-Bicocca, Italy
5Institute of Neurosurgery, Catholic University-School of Medicine, Roma-Italy (literal)
- Titolo
- PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment (literal)
- Abstract
- Abstract
Background
Cancer stem cells (CSC) represent a rare fraction of cancer cells characterized by resistance to chemotherapy and radiation, therefore nowadays there is great need to develop new targeted therapies for brain tumors and our study aim to target pivotal transmembrane receptors such as Notch, EGFR and PDGFR, which are already under investigation in clinical trials setting for the treatment of Glioblastoma Multiforme (GBM).
Methods
MTS assay was performed to evaluate cells response to pharmacological treatments. Quantitative RT-PCR and Western blots were performed to state the expression of Notch1, EGFR and PDGFR?/? and the biological effects exerted by either single or combined targeted therapy in GBM CSC. GBM CSC invasive ability was tested in vitro in absence or presence of Notch and/or EGFR signaling inhibitors.
Results
In this study, we investigated gene expression and function of Notch1, EGFR and PDGFR to determine their role among GBM tumor core- (c-CSC) vs. peritumor tissue-derived cancer stem cells (p-CSC) of six cases of GBM. Notch inhibition significantly impaired cell growth of c-CSC compared to p-CSC pools, with no effects observed in cell cycle distribution, apoptosis and cell invasion assays. Instead, anti-EGFR therapy induced cell cycle arrest, sometimes associated with apoptosis and reduction of cell invasiveness in GBM CSC. In two cases, c-CSC pools were more sensitive to simultaneous anti-Notch and anti-EGFR treatment than either therapy alone compared to p-CSC, which were mostly resistant to treatment. We reported the overexpression of PDGFR? and its up-regulation following anti-EGFR therapy in GBM p-CSC compared to c-CSC. RNA interference of PDGFR? significantly reduced cell proliferation rate of p-CSC, while its pharmacological inhibition with Crenolanib impaired survival of both CSC pools, whose effects in combination with EGFR inhibition were maximized.
Conclusions
We have used different drugs combination to identify the more effective therapeutic targets for GBM CSC, particularly against GBM peritumor tissue-derived CSC, which are mostly resistant to treatments. Overall, our results provide the rationale for simultaneous targeting of EGFR and PDGFR, which would be beneficial in the treatment of GBM. (literal)
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