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Erschienen in: Journal of Neuro-Oncology 3/2018

08.06.2018 | Laboratory Investigation

Evaluation of radiation-related invasion in primary patient-derived glioma cells and validation with established cell lines: impact of different radiation qualities with differing LET

verfasst von: M. Wank, D. Schilling, J. Reindl, B. Meyer, J. Gempt, S. Motov, F. Alexander, J. J. Wilkens, J. Schlegel, T. E. Schmid, S. E. Combs

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2018

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Abstract

Purpose

Glioblastoma multiforme (GBM) is the most common primary brain tumor and has a very poor overall prognosis. Multimodal treatment is still inefficient and one main reason is the invasive nature of GBM cells, enabling the tumor cells to escape from the treatment area causing tumor progression. This experimental study describes the effect of low- and high-LET irradiation on the invasion of primary GBM cells with a validation in established cell systems.

Methods

Seven patient derived primary GBM as well as three established cell lines (LN229, LN18 and U87) were used in this study. Invasion was investigated using Matrigel® coated transwell chambers. Irradiation was performed with low- (X-ray) and high-LET (alpha particles) radiation. The colony formation assay was chosen to determine the corresponding alpha particle dose equivalent to the X-ray dose.

Results

4 Gy X-ray irradiation increased the invasive potential of six patient derived GBM cells as well as two of the established lines. In contrast, alpha particle irradiation with an equivalent dose of 1.3 Gy did not show any effect on the invasive behavior. The findings were validated with established cell lines.

Conclusion

Our results show that in contrast to low-LET irradiation high-LET irradiation does not enhance the invasion of established and primary glioblastoma cell lines. We therefore suggest that high-LET irradiation could become an alternative treatment option. To fully exploit the benefits of high-LET irradiation concerning the invasion of GBM further molecular studies should be performed.
Literatur
2.
Zurück zum Zitat Hou LC, Veeravagu A, Hsu AR, Tse VC (2006) Recurrent glioblastoma multiforme: a review of natural history and management options. Neurosurg Focus 20(4):E5CrossRefPubMed Hou LC, Veeravagu A, Hsu AR, Tse VC (2006) Recurrent glioblastoma multiforme: a review of natural history and management options. Neurosurg Focus 20(4):E5CrossRefPubMed
5.
Zurück zum Zitat Fitzek MM, Thornton AF, Harsh G, Rabinov JD, Munzenrider JE, Lev M, Ancukiewicz M, Bussiere M, Hedley-Whyte ET, Hochberg FH, Pardo FS (2001) Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial. Int J Radiat Oncol Biol Phys 51(1):131–137CrossRefPubMed Fitzek MM, Thornton AF, Harsh G, Rabinov JD, Munzenrider JE, Lev M, Ancukiewicz M, Bussiere M, Hedley-Whyte ET, Hochberg FH, Pardo FS (2001) Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial. Int J Radiat Oncol Biol Phys 51(1):131–137CrossRefPubMed
7.
Zurück zum Zitat Curran Jr WJC, Scott CB, Weinstein AS, Martin LA, Nelson JS, Phillips TL, Murray K, Fischbach AJ, Yakar D, Schwade JG (1993) Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83–02. J Clin Oncol 11(5):857–862. https://doi.org/10.1200/jco.1993.11.5.857 CrossRef Curran Jr WJC, Scott CB, Weinstein AS, Martin LA, Nelson JS, Phillips TL, Murray K, Fischbach AJ, Yakar D, Schwade JG (1993) Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83–02. J Clin Oncol 11(5):857–862. https://​doi.​org/​10.​1200/​jco.​1993.​11.​5.​857 CrossRef
10.
Zurück zum Zitat von Essen CF (1991) Radiation enhancement of metastasis: a review. Clin Exp Metastasis 9(2):77–104CrossRef von Essen CF (1991) Radiation enhancement of metastasis: a review. Clin Exp Metastasis 9(2):77–104CrossRef
15.
Zurück zum Zitat Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61(3):215–225 (discussion 226–219)CrossRefPubMed Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61(3):215–225 (discussion 226–219)CrossRefPubMed
16.
Zurück zum Zitat Hirota Y, Masunaga S, Kondo N, Kawabata S, Hirakawa H, Yajima H, Fujimori A, Ono K, Kuroiwa T, Miyatake S (2014) High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation. J Radiat Res 55(1):75–83. https://doi.org/10.1093/jrr/rrt095 CrossRefPubMed Hirota Y, Masunaga S, Kondo N, Kawabata S, Hirakawa H, Yajima H, Fujimori A, Ono K, Kuroiwa T, Miyatake S (2014) High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation. J Radiat Res 55(1):75–83. https://​doi.​org/​10.​1093/​jrr/​rrt095 CrossRefPubMed
18.
Zurück zum Zitat Combs SE, Kieser M, Rieken S, Habermehl D, Jakel O, Haberer T, Nikoghosyan A, Haselmann R, Unterberg A, Wick W, Debus J (2010) Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer 10:478. https://doi.org/10.1186/1471-2407-10-478 CrossRefPubMedPubMedCentral Combs SE, Kieser M, Rieken S, Habermehl D, Jakel O, Haberer T, Nikoghosyan A, Haselmann R, Unterberg A, Wick W, Debus J (2010) Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer 10:478. https://​doi.​org/​10.​1186/​1471-2407-10-478 CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Roos H, Kellerer AM (1989) Design criteria and performance parameters of an alpha irradiation device for cell studies. Phys Med Biol 34(12):1823CrossRef Roos H, Kellerer AM (1989) Design criteria and performance parameters of an alpha irradiation device for cell studies. Phys Med Biol 34(12):1823CrossRef
22.
23.
Zurück zum Zitat Park CM, Park MJ, Kwak HJ, Lee HC, Kim MS, Lee SH, Park IC, Rhee CH, Hong SI (2006) Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 66(17):8511–8519. https://doi.org/10.1158/0008-5472.can-05-4340 CrossRefPubMed Park CM, Park MJ, Kwak HJ, Lee HC, Kim MS, Lee SH, Park IC, Rhee CH, Hong SI (2006) Ionizing radiation enhances matrix metalloproteinase-2 secretion and invasion of glioma cells through Src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signaling pathways. Cancer Res 66(17):8511–8519. https://​doi.​org/​10.​1158/​0008-5472.​can-05-4340 CrossRefPubMed
27.
Zurück zum Zitat Ogata T, Teshima T, Inaoka M, Minami K, Tsuchiya T, Isono M, Furusawa Y, Matsuura N (2011) Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway. J Radiat Res 52(3):374–379. https://doi.org/10.1269/jrr.10102 CrossRefPubMed Ogata T, Teshima T, Inaoka M, Minami K, Tsuchiya T, Isono M, Furusawa Y, Matsuura N (2011) Carbon Ion Irradiation Suppresses Metastatic Potential of Human Non-small Cell Lung Cancer A549 Cells through the Phosphatidylinositol-3-Kinase/Akt Signaling Pathway. J Radiat Res 52(3):374–379. https://​doi.​org/​10.​1269/​jrr.​10102 CrossRefPubMed
30.
Zurück zum Zitat Barazzuol L, Jena R, Burnet NG, Jeynes JC, Merchant MJ, Kirkby KJ, Kirkby NF (2012) In vitro evaluation of combined temozolomide and radiotherapy using X rays and high-linear energy transfer radiation for glioblastoma. Radiat Res 177(5):651–662CrossRefPubMed Barazzuol L, Jena R, Burnet NG, Jeynes JC, Merchant MJ, Kirkby KJ, Kirkby NF (2012) In vitro evaluation of combined temozolomide and radiotherapy using X rays and high-linear energy transfer radiation for glioblastoma. Radiat Res 177(5):651–662CrossRefPubMed
Metadaten
Titel
Evaluation of radiation-related invasion in primary patient-derived glioma cells and validation with established cell lines: impact of different radiation qualities with differing LET
verfasst von
M. Wank
D. Schilling
J. Reindl
B. Meyer
J. Gempt
S. Motov
F. Alexander
J. J. Wilkens
J. Schlegel
T. E. Schmid
S. E. Combs
Publikationsdatum
08.06.2018
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2923-4

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