Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/29036
Title: | The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation | Authors: | Konings, Katrien Vandevoorde, Chariot BELMANS, Niels Vermeesen, Randy Baselet, Bjorn Van Walleghem, Merel Janssen, Ann Isebaert, Sofie Baatout, Sarah Haustermans, Karin MOREELS, Marjan |
Issue Date: | 2019 | Publisher: | FRONTIERS MEDIA SA | Source: | FRONTIERS IN ONCOLOGY, 9 (Art N° 391) | Abstract: | Due to the advantages of charged particles compared to conventional radiotherapy, a vast increase is noted in the use of particle therapy in the clinic. These advantages include an improved dose deposition and increased biological effectiveness. Metastasis is still an important cause of mortality in cancer patients and evidence has shown that conventional radiotherapy can increase the formation of metastasizing cells. An important pathway involved in the process of metastasis is the Hedgehog (Hh) signaling pathway. Recent studies have demonstrated that activation of the Hh pathway, in response to X-rays, can lead to radioresistance and increased migratory, and invasive capabilities of cancer cells. Here, we investigated the effect of X-rays, protons, and carbon ions on cell survival, migration, and Hh pathway gene expression in prostate cancer (PC3) and medulloblastoma (DAOY) cell lines. In addition, the potential modulation of cell survival and migration by the Hh pathway inhibitor GANT61 was investigated. We found that in both cell lines, carbon ions were more effective in decreasing cell survival and migration as well as inducing more significant alterations in the Hh pathway genes compared to X-rays or protons. In addition, we show here for the first time that the Hh inhibitor GANT61 is able to sensitize DAOY medulloblastoma cells to particle radiation (proton and carbon ion) but not to conventional X-rays. This important finding demonstrates that the results of combination treatment strategies with X-ray radiotherapy cannot be automatically extrapolated to particle therapy and should be investigated separately. In conclusion, combining GANT61 with particle radiation could offer a benefit for specific cancer types with regard to cancer cell survival. | Notes: | [Konings, Katrien; Belmans, Niels; Vermeesen, Randy; Baselet, Bjorn; Van Walleghem, Merel; Janssen, Ann; Baatout, Sarah; Moreels, Marjan] Belgian Nucl Res Ctr SCK CEN, Inst Environm Hlth & Safety, Radiobiol Unit, Mol, Belgium. [Konings, Katrien; Isebaert, Sofie; Haustermans, Karin] Katholieke Univ Leuven, Dept Oncol, Lab Expt Radiotherapy, Leuven, Belgium. [Vandevoorde, Chariot] NRF iThemba LABS, Radiat Biophys Div, Faure, South Africa. [Belmans, Niels] Hasselt Univ, Biomed Res Inst BIOMED, Lab Morphol, Diepenbeek, Belgium. [Isebaert, Sofie; Haustermans, Karin] Univ Hosp Leuven, Dept Radiat Oncol, Leuven, Belgium. | Keywords: | particle therapy; proton; carbon ion; radiosensitization; Hedgehog pathway; migration; gene expression; GANT61;particle therapy; proton; carbon ion; radiosensitization; Hedgehog pathway; migration; gene expression; GANT61 | Document URI: | http://hdl.handle.net/1942/29036 | ISSN: | 2234-943X | e-ISSN: | 2234-943X | DOI: | 10.3389/fonc.2019.00391 | ISI #: | 000467873000001 | Rights: | 2019 Konings, Vandevoorde, Belmans, Vermeesen, Baselet, Walleghem, Janssen, Isebaert, Baatout, Haustermans and Moreels. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
konings 1.pdf | Published version | 2.6 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
3
checked on Sep 3, 2020
WEB OF SCIENCETM
Citations
21
checked on Oct 14, 2024
Page view(s)
100
checked on Sep 7, 2022
Download(s)
146
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.