title: Effects of single or combined treatments with radiation and chemotherapy on survival and danger signals expression in glioblastoma cell lines.
abstract: The success of chemo- and radiotherapy in glioblastoma multiforme, the most common and lethal primary brain tumour, could rely on the induction of immunogenic tumour cell death and on the induction of anticancer immune response. In this study we investigated cell survival to single treatments or combination of X-rays and temozolomide in glioblastoma cell lines (T98G and U251MG) and we attempted to identify danger signals (HMGB1 and HSP70) released by dying cells in the microenvironment that could activate antitumour immunity contributing to the therapeutic efficacy of conventional treatments. Our data suggest that HSP70 translocates from cytoplasm to extracellular environment after an increase in radiation dose and HMGB1 translocates from the nucleus to the cytoplasm and subsequently is released into the extracellular space, confirming a role of these proteins as signals released after radiation-induced damage in glioblastoma cells. We also could state that TMZ had limited effectiveness in activating HMGB1 and HSP70 signalling and, instead, an adjuvant effect was observed in some combined treatments, depending on schedule, cell line, and timing. A big challenge in tumour therapy is, therefore, to identify the most beneficial combination and chronology of multiple treatment options to contribute to the improvement of the therapeutic outcome.
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pasi
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy ; Department of Medical Physics, IRCCS Policlinico S. Matteo Foundation, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Alessandro
authors.identifier: 0000-0003-4354-9100
authors.initials: A
authors.lastname: Paolini
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Nano
authors.affiliation: Department of Medical Physics, IRCCS Policlinico S. Matteo Foundation, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Di Liberto
authors.affiliation: Department of Earth and Environmental Sciences, University of Pavia, Via Ferrata 1, 27100 Pavia, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Capelli
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D024243:HMGB1 Protein / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D000077204:Temozolomide; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D018840:HSP70 Heat-Shock Proteins; D003606:Dacarbazine; D000077204:Temozolomide
references.citation: Cell Stress Chaperones. 2003 Spring;8(1):26-36
references.pmid: 12820652
references.citation: Eur J Immunol. 2005 Sep;35(9):2518-27
references.pmid: 16144035
references.citation: Int J Radiat Oncol Biol Phys. 2000 Jun 1;47(3):779-84
references.pmid: 10837964
references.citation: Clin Cancer Res. 2007 May 15;13(10):2836-48
references.pmid: 17504981
references.citation: Cancer Metastasis Rev. 2011 Mar;30(1):61-9
references.pmid: 21249425
references.citation: Anticancer Res. 2011 Nov;31(11):3727-31
references.pmid: 22110193
references.citation: Curr Opin Immunol. 2008 Oct;20(5):504-11
references.pmid: 18573340
references.citation: EMBO Rep. 2004 Aug;5(8):825-30
references.pmid: 15272298
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):931-8
references.pmid: 18245557
references.citation: J Neurooncol. 2004 Nov;70(2):137-60
references.pmid: 15674475
references.citation: Nat Rev Immunol. 2008 Apr;8(4):279-89
references.pmid: 18340345
references.citation: J Neurooncol. 2009 Oct;95(1):13-22
references.pmid: 19381445
references.citation: Am J Physiol Cell Physiol. 2006 Dec;291(6):C1318-25
references.pmid: 16855214
references.citation: J Clin Invest. 2008 Jun;118(6):1991-2001
references.pmid: 18523649
references.citation: Mutat Res. 2010 Feb 3;684(1-2):81-9
references.pmid: 20026341
references.citation: Cancer Cell. 2007 Oct;12(4):300-1
references.pmid: 17936555
references.citation: PLoS Med. 2009 Jan 13;6(1):e10
references.pmid: 19143470
references.citation: Oncology (Williston Park). 2008 Aug;22(9):1064-70; discussion 1075, 1080-1, 1084
references.pmid: 18777956
references.citation: J Biol Chem. 2002 Mar 1;277(9):7157-64
references.pmid: 11748232
references.citation: Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1511-9
references.pmid: 19931733
references.citation: Am J Physiol Cell Physiol. 2003 Apr;284(4):C870-9
references.pmid: 12620891
references.citation: Anticancer Drugs. 1997 Jan;8(1):92-7
references.pmid: 9147618
references.citation: Immunol Rev. 2007 Dec;220:47-59
references.pmid: 17979839
references.citation: Clin Cancer Res. 2008 Mar 15;14(6):1603-8
references.pmid: 18347160
references.citation: J Neurooncol. 2008 Mar;87(1):23-33
references.pmid: 17975708
references.citation: Int J Oncol. 2004 Sep;25(3):777-85
references.pmid: 15289883
references.citation: Cell Stress Chaperones. 2008 Spring;13(1):1-10
references.pmid: 18347936