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Article

Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines

1
Department of Neurology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2-4, 710204 Craiova, Romania
2
Department of Pharmacological Technology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2-4, 710204 Craiova, Romania
3
Karolinska Institutet, Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Z1:00, 171 76 Stockholm, Sweden
4
Department of Biochemistry, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2-4, 710204 Craiova, Romania
5
Department of Physiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Str. Petru Rares nr. 2-4, 710204 Craiova, Romania
6
Department of Neurosurgery, “Bagdasar-Arseni” Emergency Hospital, Soseaua Berceni 12, 041915 Bucharest, Romania
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4663; https://doi.org/10.3390/ijms20194663
Received: 19 August 2019 / Revised: 14 September 2019 / Accepted: 19 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue Kinase Signal Transduction 2020)
Treatment of high grade gliomas (HGGs) has remained elusive due to their high heterogeneity and aggressiveness. Surgery followed by radiotherapy represents the mainstay of treatment for HGG. However, the unfavorable location of the tumor that usually limits total resection and the resistance to radiation therapy are the major therapeutic problems. Chemotherapy with DNA alkylating agent temozolomide is also used to treat HGG, despite modest effects on survival. Disregulation of several growth factor receptors (GFRs) were detected in HGG and receptor amplification in glioblastoma has been suggested to be responsible for heterogeneity propagation through clonal evolution. Molecularly targeted agents inhibiting these membrane proteins have demonstrated significant cytotoxicity in several types of cancer cells when tested in preclinical models. Platelet-derived growth factor receptors (PDGFRs) and associated signaling were found to be implicated in gliomagenesis, moreover, HGG commonly display a Platelet-derived growth factor (PDGF) autocrine pathway that is not present in normal brain tissues. We have previously shown that both the susceptibility towards PDGFR and the impact of the PDGFR inactivation on the radiation response were different in different HGG cell lines. Therefore, we decided to extend our investigation, using two other HGG cell lines that express PDGFR at the cell surface. Here, we investigated the effect of PDGFR inhibition alone or in combination with gamma radiation in 11 and 15 HGG cell lines. Our results showed that while targeting the PDGFR represents a good means of treatment in HGG, the combination of receptor inhibition with gamma radiation did not result in any discernable difference compared to the single treatment. The PI3K/PTEN/Akt/mTOR and Ras/Raf/MEK/ERK pathways are the major signaling pathways emerging from the GFRs, including PDGFR. Decreased sensitivity to radiation-induced cell death are often associated with redundancy in these pro-survival signaling pathways. Here we found that Phosphoinositide 3-kinases (PI3K), Extracellular-signal-regulated kinase 1/2 (ERK1/2), or c-Jun N-terminal kinase 1/2 (JNK1/2) inactivation induced radiosensitivity in HGG cells. View Full-Text
Keywords: high grade glioma; radiotherapy; Platelet-derived growth factor receptor (PDGFR) high grade glioma; radiotherapy; Platelet-derived growth factor receptor (PDGFR)
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MDPI and ACS Style

Alexandru, O.; Sevastre, A.-S.; Castro, J.; Artene, S.-A.; Tache, D.E.; Purcaru, O.S.; Sfredel, V.; Tataranu, L.G.; Dricu, A. Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines. Int. J. Mol. Sci. 2019, 20, 4663. https://doi.org/10.3390/ijms20194663

AMA Style

Alexandru O, Sevastre A-S, Castro J, Artene S-A, Tache DE, Purcaru OS, Sfredel V, Tataranu LG, Dricu A. Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines. International Journal of Molecular Sciences. 2019; 20(19):4663. https://doi.org/10.3390/ijms20194663

Chicago/Turabian Style

Alexandru, Oana, Ani-Simona Sevastre, Juan Castro, Stefan-Alexandru Artene, Daniela E. Tache, Oana S. Purcaru, Veronica Sfredel, Ligia G. Tataranu, and Anica Dricu. 2019. "Platelet-Derived Growth Factor Receptor and Ionizing Radiation in High Grade Glioma Cell Lines" International Journal of Molecular Sciences 20, no. 19: 4663. https://doi.org/10.3390/ijms20194663

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