Skip to main content
Top
Published in: Clinical and Experimental Medicine 3/2018

Open Access 01-08-2018 | Original Article

Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

Authors: Junfeng Liu, Qinglei Gao, Tao Xie, Yu Liu, Longjun Luo, Cheng Xu, Lu Shen, Feng Wan, Ting Lei, Fei Ye

Published in: Clinical and Experimental Medicine | Issue 3/2018

Login to get access

Abstract

Glioblastoma multiforme (GBM) is the most common malignancy in central nervous system. A small subpopulation of GBM cells known as GBM stem-like cells (GSLCs) were supposed to be the most malignant cells among GBM cells as they are resistant to multiple therapies including radiotherapy. In this study, we set up two GSLCs cell lines from the two parental U87 and U251 glioma cell lines, and studied the expression of apoptosis-related genes alteration in GSLCs before and after irradiation. We found that one of the receptors of TNF-related apoptosis-inducing ligand (TRAIL), DR5, was dramatically up-regulated in GSLCs after irradiation (IR). Although GSLCs are resistant to both TRAIL and radiation treatment alone, the combined treatment with TRAIL and irradiation achieved maximum killing effect of GSLCs due to inducing the expression of DR5 and inhibiting the expression of cFLIP. Therefore, TRAIL and IR combined treatment would be a simple but practical therapeutic strategy for clinical application.
Appendix
Available only for authorised users
Literature
2.
go back to reference Bao SD, Wu QL, McLendon RE, Hao YL, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60.CrossRefPubMed Bao SD, Wu QL, McLendon RE, Hao YL, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60.CrossRefPubMed
3.
go back to reference Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 2006;5:67.CrossRefPubMedPubMedCentral Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, et al. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 2006;5:67.CrossRefPubMedPubMedCentral
4.
go back to reference Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.CrossRefPubMed Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11.CrossRefPubMed
6.
go back to reference Schulenburg A, Blatt K, Cerny-Reiterer S, Sadovnik I, Herrmann H, Marian B, et al. Cancer stem cells in basic science and in translational oncology: can we translate into clinical application? J Hematol Oncol. 2015;8:16.CrossRefPubMedPubMedCentral Schulenburg A, Blatt K, Cerny-Reiterer S, Sadovnik I, Herrmann H, Marian B, et al. Cancer stem cells in basic science and in translational oncology: can we translate into clinical application? J Hematol Oncol. 2015;8:16.CrossRefPubMedPubMedCentral
7.
go back to reference Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28(1):17–28.PubMedPubMedCentral Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, et al. Notch promotes radioresistance of glioma stem cells. Stem Cells. 2010;28(1):17–28.PubMedPubMedCentral
8.
go back to reference Kim Y, Kim KH, Lee J, Lee YA, Kim M, Lee SJ, et al. Wnt activation is implicated in glioblastoma radioresistance. Lab Invest. 2012;92(3):466–73.CrossRefPubMed Kim Y, Kim KH, Lee J, Lee YA, Kim M, Lee SJ, et al. Wnt activation is implicated in glioblastoma radioresistance. Lab Invest. 2012;92(3):466–73.CrossRefPubMed
9.
go back to reference Santoni M, Burattini L, Nabissi M, Morelli MB, Berardi R, Santoni G, et al. Essential role of Gli proteins in glioblastoma multiforme. Curr Protein Pept Sci. 2013;14(2):133–40.CrossRefPubMed Santoni M, Burattini L, Nabissi M, Morelli MB, Berardi R, Santoni G, et al. Essential role of Gli proteins in glioblastoma multiforme. Curr Protein Pept Sci. 2013;14(2):133–40.CrossRefPubMed
10.
go back to reference Kim SH, Ezhilarasan R, Phillips E, Gallego-Perez D, Sparks A, Taylor D, et al. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner. Cancer Cell. 2016;29(2):201–13.CrossRefPubMedPubMedCentral Kim SH, Ezhilarasan R, Phillips E, Gallego-Perez D, Sparks A, Taylor D, et al. Serine/threonine kinase MLK4 determines mesenchymal identity in glioma stem cells in an NF-kappaB-dependent manner. Cancer Cell. 2016;29(2):201–13.CrossRefPubMedPubMedCentral
11.
12.
go back to reference Fulda S. Inhibitor of apoptosis (IAP) proteins as therapeutic targets for radiosensitization of human cancers. Cancer Treat Rev. 2012;38(6):760–6.CrossRefPubMed Fulda S. Inhibitor of apoptosis (IAP) proteins as therapeutic targets for radiosensitization of human cancers. Cancer Treat Rev. 2012;38(6):760–6.CrossRefPubMed
13.
go back to reference Shinomiya N. New concepts in radiation-induced apoptosis: ‘premitotic apoptosis’ and ‘postmitotic apoptosis’. J Cell Mol Med. 2001;5(3):240–53.CrossRefPubMed Shinomiya N. New concepts in radiation-induced apoptosis: ‘premitotic apoptosis’ and ‘postmitotic apoptosis’. J Cell Mol Med. 2001;5(3):240–53.CrossRefPubMed
14.
go back to reference Senbabaoglu F, Cingoz A, Kaya E, Kazancioglu S, Lack NA, Acilan C, et al. Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme. Cancer Biol Ther. 2016;17(5):546–57.CrossRefPubMedPubMedCentral Senbabaoglu F, Cingoz A, Kaya E, Kazancioglu S, Lack NA, Acilan C, et al. Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme. Cancer Biol Ther. 2016;17(5):546–57.CrossRefPubMedPubMedCentral
15.
go back to reference Prasad S, Kim JH, Gupta SC, Aggarwal BB. Targeting death receptors for TRAIL by agents designed by Mother Nature. Trends Pharmacol Sci. 2014;35(10):520–36.CrossRefPubMed Prasad S, Kim JH, Gupta SC, Aggarwal BB. Targeting death receptors for TRAIL by agents designed by Mother Nature. Trends Pharmacol Sci. 2014;35(10):520–36.CrossRefPubMed
16.
go back to reference Yu CC, Chiou GY, Lee YY, Chang YL, Huang PI, Cheng YW, et al. Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity. Childs Nerv Syst. 2010;26(7):897–904.CrossRefPubMed Yu CC, Chiou GY, Lee YY, Chang YL, Huang PI, Cheng YW, et al. Medulloblastoma-derived tumor stem-like cells acquired resistance to TRAIL-induced apoptosis and radiosensitivity. Childs Nerv Syst. 2010;26(7):897–904.CrossRefPubMed
17.
go back to reference Henrich CJ, Brooks AD, Erickson KL, Thomas CL, Bokesch HR, Tewary P, et al. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation. Cell Death Dis. 2015;6:e1666.CrossRefPubMedPubMedCentral Henrich CJ, Brooks AD, Erickson KL, Thomas CL, Bokesch HR, Tewary P, et al. Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation. Cell Death Dis. 2015;6:e1666.CrossRefPubMedPubMedCentral
18.
go back to reference Dao P, Smith N, Scott-Algara D, Garbay C, Herbeuval JP, Chen H. Restoration of TRAIL-induced apoptosis in resistant human pancreatic cancer cells by a novel FAK inhibitor, PH11. Cancer Lett. 2015;360(1):48–59.CrossRefPubMed Dao P, Smith N, Scott-Algara D, Garbay C, Herbeuval JP, Chen H. Restoration of TRAIL-induced apoptosis in resistant human pancreatic cancer cells by a novel FAK inhibitor, PH11. Cancer Lett. 2015;360(1):48–59.CrossRefPubMed
19.
go back to reference Alexiou GA, Tsamis KI, Vartholomatos E, Peponi E, Tzima E, Tasiou I, et al. Combination treatment of TRAIL, DFMO and radiation for malignant glioma cells. J Neurooncol. 2015;123(2):217–24.CrossRefPubMed Alexiou GA, Tsamis KI, Vartholomatos E, Peponi E, Tzima E, Tasiou I, et al. Combination treatment of TRAIL, DFMO and radiation for malignant glioma cells. J Neurooncol. 2015;123(2):217–24.CrossRefPubMed
20.
go back to reference Wu X, Lippman SM. An intermittent approach for cancer chemoprevention. Nat Rev Cancer. 2011;11(12):879–85.CrossRefPubMed Wu X, Lippman SM. An intermittent approach for cancer chemoprevention. Nat Rev Cancer. 2011;11(12):879–85.CrossRefPubMed
21.
go back to reference Abdulghani J, El-Deiry WS. TRAIL receptor signaling and therapeutics. Expert Opin Ther Target. 2010;14(10):1091–108.CrossRef Abdulghani J, El-Deiry WS. TRAIL receptor signaling and therapeutics. Expert Opin Ther Target. 2010;14(10):1091–108.CrossRef
22.
go back to reference Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104(2):155–62.CrossRefPubMedPubMedCentral Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104(2):155–62.CrossRefPubMedPubMedCentral
23.
go back to reference Ding L, Yuan C, Wei F, Wang G, Zhang J, Bellail AC, et al. Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP. Cancer Invest. 2011;29(8):511–20.CrossRefPubMedPubMedCentral Ding L, Yuan C, Wei F, Wang G, Zhang J, Bellail AC, et al. Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP. Cancer Invest. 2011;29(8):511–20.CrossRefPubMedPubMedCentral
24.
go back to reference Xiao QG, Tan YH, Guo Y, Yang HK, Mao F, Xie RF, et al. Soluble LRIG2 ectodomain is released from glioblastoma cells and promotes the proliferation and inhibits the apoptosis of glioblastoma cells in vitro and in vivo in a similar manner to the full-length LRIG2. PLoS One. 2014;9(10):e111419.CrossRefPubMedPubMedCentral Xiao QG, Tan YH, Guo Y, Yang HK, Mao F, Xie RF, et al. Soluble LRIG2 ectodomain is released from glioblastoma cells and promotes the proliferation and inhibits the apoptosis of glioblastoma cells in vitro and in vivo in a similar manner to the full-length LRIG2. PLoS One. 2014;9(10):e111419.CrossRefPubMedPubMedCentral
25.
go back to reference Kim SM, Oh JH, Park SA, Ryu CH, Lim JY, Kim DS, et al. Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy. Stem Cells. 2010;28(12):2217–28.CrossRefPubMed Kim SM, Oh JH, Park SA, Ryu CH, Lim JY, Kim DS, et al. Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy. Stem Cells. 2010;28(12):2217–28.CrossRefPubMed
26.
go back to reference Capper D, Gaiser T, Hartmann C, Habel A, Mueller W, Herold-Mende C, et al. Stem-cell-like glioma cells are resistant to TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation. Acta Neuropathol. 2009;117(4):445–56.CrossRefPubMed Capper D, Gaiser T, Hartmann C, Habel A, Mueller W, Herold-Mende C, et al. Stem-cell-like glioma cells are resistant to TRAIL/Apo2L and exhibit down-regulation of caspase-8 by promoter methylation. Acta Neuropathol. 2009;117(4):445–56.CrossRefPubMed
27.
go back to reference Geismann C, Grohmann F, Sebens S, Wirths G, Dreher A, Hasler R, et al. c-Rel is a critical mediator of NF-kappaB-dependent TRAIL resistance of pancreatic cancer cells. Cell Death Dis. 2014;5:e1455.CrossRefPubMedPubMedCentral Geismann C, Grohmann F, Sebens S, Wirths G, Dreher A, Hasler R, et al. c-Rel is a critical mediator of NF-kappaB-dependent TRAIL resistance of pancreatic cancer cells. Cell Death Dis. 2014;5:e1455.CrossRefPubMedPubMedCentral
28.
go back to reference Kazimirsky G, Jiang W, Slavin S, Ziv-Av A, Brodie C. Mesenchymal stem cells enhance the oncolytic effect of Newcastle disease virus in glioma cells and glioma stem cells via the secretion of TRAIL. Stem Cell Res Ther. 2016;7(1):149.CrossRefPubMedPubMedCentral Kazimirsky G, Jiang W, Slavin S, Ziv-Av A, Brodie C. Mesenchymal stem cells enhance the oncolytic effect of Newcastle disease virus in glioma cells and glioma stem cells via the secretion of TRAIL. Stem Cell Res Ther. 2016;7(1):149.CrossRefPubMedPubMedCentral
29.
go back to reference Im CN, Yun HH, Song B, Youn DY, Cui MN, Kim HS, et al. BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes. Oncotarget. 2016;7(23):35056–70.CrossRefPubMedPubMedCentral Im CN, Yun HH, Song B, Youn DY, Cui MN, Kim HS, et al. BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes. Oncotarget. 2016;7(23):35056–70.CrossRefPubMedPubMedCentral
30.
go back to reference Rosa P, Sforna L, Carlomagno S, Mangino G, Miscusi M, Pessia M, et al. Overexpression of large-conductance calcium-activated potassium channels in human glioblastoma stem-like cells and their role in cell migration. J Cell Physiol. 2017;232(9):2478–88.CrossRefPubMed Rosa P, Sforna L, Carlomagno S, Mangino G, Miscusi M, Pessia M, et al. Overexpression of large-conductance calcium-activated potassium channels in human glioblastoma stem-like cells and their role in cell migration. J Cell Physiol. 2017;232(9):2478–88.CrossRefPubMed
31.
go back to reference Oh SJ, Yang JI, Kim O, Ahn EJ, Kang WD, Lee JH, et al. Human U87 glioblastoma cells with stemness features display enhanced sensitivity to natural killer cell cytotoxicity through altered expression of NKG2D ligand. Cancer Cell Int. 2017;17:22.CrossRefPubMedPubMedCentral Oh SJ, Yang JI, Kim O, Ahn EJ, Kang WD, Lee JH, et al. Human U87 glioblastoma cells with stemness features display enhanced sensitivity to natural killer cell cytotoxicity through altered expression of NKG2D ligand. Cancer Cell Int. 2017;17:22.CrossRefPubMedPubMedCentral
32.
go back to reference Choy W, Nagasawa DT, Trang A, Thill K, Spasic M, Yang I. CD133 as a marker for regulation and potential for targeted therapies in glioblastoma multiforme. Neurosurg Clin N Am. 2012;23(3):391.CrossRefPubMed Choy W, Nagasawa DT, Trang A, Thill K, Spasic M, Yang I. CD133 as a marker for regulation and potential for targeted therapies in glioblastoma multiforme. Neurosurg Clin N Am. 2012;23(3):391.CrossRefPubMed
33.
go back to reference Grosse-Gehling P, Fargeas CA, Dittfeld C, Garbe Y, Alison MR, Corbeil D, et al. CD133 as a biomarker for putative cancer stem cells in solid tumours: limitations, problems and challenges. J Pathol. 2013;229(3):355–78.CrossRefPubMed Grosse-Gehling P, Fargeas CA, Dittfeld C, Garbe Y, Alison MR, Corbeil D, et al. CD133 as a biomarker for putative cancer stem cells in solid tumours: limitations, problems and challenges. J Pathol. 2013;229(3):355–78.CrossRefPubMed
34.
go back to reference Ramasamy S, Narayanan G, Sankaran S, Yu YH, Ahmed S. Neural stem cell survival factors. Arch Biochem Biophys. 2013;534(1–2):71–87.CrossRefPubMed Ramasamy S, Narayanan G, Sankaran S, Yu YH, Ahmed S. Neural stem cell survival factors. Arch Biochem Biophys. 2013;534(1–2):71–87.CrossRefPubMed
35.
go back to reference Schlegel CR, Fonseca AV, Stocker S, Georgiou ML, Misterek MB, Munro CE, et al. DAPK2 is a novel modulator of TRAIL-induced apoptosis. Cell Death Differ. 2014;21(11):1780–91.CrossRefPubMedPubMedCentral Schlegel CR, Fonseca AV, Stocker S, Georgiou ML, Misterek MB, Munro CE, et al. DAPK2 is a novel modulator of TRAIL-induced apoptosis. Cell Death Differ. 2014;21(11):1780–91.CrossRefPubMedPubMedCentral
36.
go back to reference Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, et al. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388(6638):190–5.CrossRefPubMed Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, et al. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388(6638):190–5.CrossRefPubMed
37.
go back to reference Lacour S, Hammann A, Wotawa A, Corcos L, Solary E, Dimanche-Boitrel MT. Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. Cancer Res. 2001;61(4):1645–51.PubMed Lacour S, Hammann A, Wotawa A, Corcos L, Solary E, Dimanche-Boitrel MT. Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. Cancer Res. 2001;61(4):1645–51.PubMed
Metadata
Title
Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells
Authors
Junfeng Liu
Qinglei Gao
Tao Xie
Yu Liu
Longjun Luo
Cheng Xu
Lu Shen
Feng Wan
Ting Lei
Fei Ye
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Clinical and Experimental Medicine / Issue 3/2018
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-018-0504-7

Other articles of this Issue 3/2018

Clinical and Experimental Medicine 3/2018 Go to the issue