Pivotal Role of PDGFR alpha in anti-Notch1 and EGFR Resistant Cancer Stem Cells Derived from Peritumor Tissue of Glioblastoma Multiforme. (Abstract/Poster in convegno)

Type
Label
  • Pivotal Role of PDGFR alpha in anti-Notch1 and EGFR Resistant Cancer Stem Cells Derived from Peritumor Tissue of Glioblastoma Multiforme. (Abstract/Poster in convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • 1Cenciarelli C., 1Manuela Zonfrillo M., 1Pierimarchi P., 2Paldino E., 2CasalboreP., 2 Felsani A., 3Vescovi AL., 4 Maira G., and 4 Mangiola A. (2014)
    Pivotal Role of PDGFR alpha in anti-Notch1 and EGFR Resistant Cancer Stem Cells Derived from Peritumor Tissue of Glioblastoma Multiforme.
    in Internationa Neuroscience Congress, 2nd Edition. Advances in Biology and Treatment of malignant Brain Glioma, Tempio di Adriano, Roma, 12-13 june 2014
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • 1Cenciarelli C., 1Manuela Zonfrillo M., 1Pierimarchi P., 2Paldino E., 2CasalboreP., 2 Felsani A., 3Vescovi AL., 4 Maira G., and 4 Mangiola A. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Abstract 06, pag. 11 (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Institute of Translational Pharmacology-CNR, Roma-Italy 2Institute of Cell Biology and Neurobiology-Roma-Italy, 3Department of Biotechnologies and Biosciences, University of Milan-Bicocca, Italy, 4Institute of Neurosurgery, Catholic University-School of Medicine, Roma-Italy (literal)
Titolo
  • Pivotal Role of PDGFR alpha in anti-Notch1 and EGFR Resistant Cancer Stem Cells Derived from Peritumor Tissue of Glioblastoma Multiforme. (literal)
Abstract
  • Introduction Nowadays there is need to develop new targeted therapies for brain tumors and therefore we aim to target transmembrane receptors such as Notch1, EGFR and PDGFR, which are already under investigation in clinical trials for the treatment of glioblastoma multiforme. Cancer stem cells represent a rare fraction of cancer cells characterized by resistance to chemotherapy and radiation. In this study, we investigated gene expression and function of Notch1, EGFR and PDGFR to address their role among tumor core- (c-CSC) vs. peritumor tissue-derived cancer stem cells (p-CSC) of six cases of GBM. Methods MTS assay was performed to evaluate the cell response to pharmacological treatments. RT-PCR and Western blot experiments were performed to state the expression of Notch, EGFR and PDGFR?/? and to understand the biological effects exerted by single or combination of specific inhibitors in GBM CSC. GBM CSC invasive ability was tested in vitro in absence or presence of Notch1 and/or EGFR inhibitors. Results We first evaluated changes in cellular response of GBM CSC undergoing to Notch inhibitor GSI-X, either alone or along with AG1478, an EGFR inhibitor. GSI-X induces a significant decrease of cell growth preferentially in c-CSC in comparison with p-CSC, and no effects were observed in cell cycle distribution, apoptosis and cell invasion assays. AG1478 significantly reduces cell growth of either c-CSC or p-CSC pools, in particular three cases were studied more thoroughly and showed a shifting in the G1 phase of cell cycle, sometimes associated with apoptosis and loss of cell invasion. Interestingly two cases, c-CSC pools were more sensitive to simultaneous anti-Notch1 and anti-EGFR treatment than either therapy alone respect to p-CSC, which resulted mostly resistant to treatment. Of note, all p-CSC of six Cases examined showed an inherent over expression of PDGFR? compared to c-CSC, the second most frequently mutated RTK in GBM, following EGFR. RNA interference experiments and pharmacological inhibition of the endogenous PDGFR? significantly reduced cell growth rate and survivability of p-CSC. The latter effects were maximized in combination with AG1478. Conclusion These results suggest that simultaneous targeting of EGFR and PDGFR may be a better therapeutic option for a GBM therapy. (literal)
Prodotto di
Autore CNR

Incoming links:


Autore CNR di
Prodotto
data.CNR.it