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The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation

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...

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Autores principales: Konings, Katrien, Vandevoorde, Charlot, Belmans, Niels, Vermeesen, Randy, Baselet, Bjorn, Walleghem, Merel Van, Janssen, Ann, Isebaert, Sofie, Baatout, Sarah, Haustermans, Karin, Moreels, Marjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527843/
https://www.ncbi.nlm.nih.gov/pubmed/31139573
http://dx.doi.org/10.3389/fonc.2019.00391
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author Konings, Katrien
Vandevoorde, Charlot
Belmans, Niels
Vermeesen, Randy
Baselet, Bjorn
Walleghem, Merel Van
Janssen, Ann
Isebaert, Sofie
Baatout, Sarah
Haustermans, Karin
Moreels, Marjan
author_facet Konings, Katrien
Vandevoorde, Charlot
Belmans, Niels
Vermeesen, Randy
Baselet, Bjorn
Walleghem, Merel Van
Janssen, Ann
Isebaert, Sofie
Baatout, Sarah
Haustermans, Karin
Moreels, Marjan
author_sort Konings, Katrien
collection PubMed
description 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.
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spelling pubmed-65278432019-05-28 The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation Konings, Katrien Vandevoorde, Charlot Belmans, Niels Vermeesen, Randy Baselet, Bjorn Walleghem, Merel Van Janssen, Ann Isebaert, Sofie Baatout, Sarah Haustermans, Karin Moreels, Marjan Front Oncol Oncology 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. Frontiers Media S.A. 2019-05-14 /pmc/articles/PMC6527843/ /pubmed/31139573 http://dx.doi.org/10.3389/fonc.2019.00391 Text en Copyright © 2019 Konings, Vandevoorde, Belmans, Vermeesen, Baselet, Walleghem, Janssen, Isebaert, Baatout, Haustermans and Moreels. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Oncology
Konings, Katrien
Vandevoorde, Charlot
Belmans, Niels
Vermeesen, Randy
Baselet, Bjorn
Walleghem, Merel Van
Janssen, Ann
Isebaert, Sofie
Baatout, Sarah
Haustermans, Karin
Moreels, Marjan
The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
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
title_full The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
title_fullStr The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
title_full_unstemmed The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
title_short The Combination of Particle Irradiation With the Hedgehog Inhibitor GANT61 Differently Modulates the Radiosensitivity and Migration of Cancer Cells Compared to X-Ray Irradiation
title_sort combination of particle irradiation with the hedgehog inhibitor gant61 differently modulates the radiosensitivity and migration of cancer cells compared to x-ray irradiation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527843/
https://www.ncbi.nlm.nih.gov/pubmed/31139573
http://dx.doi.org/10.3389/fonc.2019.00391
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