Impact of phospholipase C β1 in glioblastoma: a study on the main mechanisms of tumor aggressiveness.


Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
18 Mar 2022
Historique:
received: 08 11 2021
accepted: 06 02 2022
revised: 21 01 2022
entrez: 18 3 2022
pubmed: 19 3 2022
medline: 5 4 2022
Statut: epublish

Résumé

Glioblastoma represents the most lethal brain tumor in adults. Several studies have shown the key role of phospholipase C β1 (PLCβ1) in the regulation of many mechanisms within the central nervous system suggesting PLCβ1 as a novel signature gene in the molecular classification of high-grade gliomas. This study aims to determine the pathological impact of PLCβ1 in glioblastoma, confirming that PLCβ1 gene expression correlates with glioma's grade, and it is lower in 50 glioblastoma samples compared to 20 healthy individuals. PLCβ1 silencing in cell lines and primary astrocytes, leads to increased cell migration and invasion, with the increment of mesenchymal transcription factors and markers, as Slug and N-Cadherin and metalloproteinases. Cell proliferation, through increased Ki-67 expression, and the main survival pathways, as β-catenin, ERK1/2 and Stat3 pathways, are also affected by PLCβ1 silencing. These data suggest a potential role of PLCβ1 in maintaining a normal or less aggressive glioma phenotype.

Identifiants

pubmed: 35303162
doi: 10.1007/s00018-022-04198-1
pii: 10.1007/s00018-022-04198-1
pmc: PMC8933313
doi:

Substances chimiques

Phospholipase C beta EC 3.1.4.11

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

195

Informations de copyright

© 2022. The Author(s).

Références

Xu S, Tang L, Li X, Fan F, Liu Z (2020) Immunotherapy for glioma: current management and future application. Cancer Lett 476:1–12. https://doi.org/10.1016/j.canlet.2020.02.002
doi: 10.1016/j.canlet.2020.02.002 pubmed: 32044356
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK et al (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1
doi: 10.1007/s00401-016-1545-1 pubmed: 27157931
Cho H-H, Park H (2017) Classification of low-grade and high-grade glioma using multi-modal image radiomics features. Annu Int Conf IEEE Eng Med Biol Soc 2017:3081–3084. https://doi.org/10.1109/EMBC.2017.8037508
doi: 10.1109/EMBC.2017.8037508
Ramirez YP, Weatherbee JL, Wheelhouse RT, Ross AH (2013) Glioblastoma multiforme therapy and mechanisms of resistance. Pharmaceuticals (Basel) 6(12):1475–1506. https://doi.org/10.3390/ph6121475
doi: 10.3390/ph6121475
Stoyanov GS, Dzhenkov D, Ghenev P, Iliev B, Enchev Y, Tonchev AB (2018) Cell biology of glioblastoma multiforme: from basic science to diagnosis and treatment. Med Oncol 35(3):27. https://doi.org/10.1007/s12032-018-1083-x
doi: 10.1007/s12032-018-1083-x pubmed: 29387965
Batash R, Asna N, Schaffer P, Francis N, Schaffer M (2017) Glioblastoma multiforme, diagnosis and treatment. Recent Lit Rev Curr Med Chem 24(27):3002–3009. https://doi.org/10.2174/0929867324666170516123206
doi: 10.2174/0929867324666170516123206
Adamson C, Kanu OO, Mehta AI, Di C, Lin N, Mattox AK et al (2009) Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs 18(8):1061–1083. https://doi.org/10.1517/13543780903052764
doi: 10.1517/13543780903052764 pubmed: 19555299
Zepecki JP, Snyder KM, Moreno MM, Fajardo E, Fiser A, Ness J et al (2019) Regulation of human glioma cell migration, tumor growth, and stemness gene expression using a Lck targeted inhibitor. Oncogene 38(10):1734–1750. https://doi.org/10.1038/s41388-018-0546-z
doi: 10.1038/s41388-018-0546-z pubmed: 30353164
Yang YR, Kang DS, Lee C, Seok H, Follo MY, Cocco L et al (2016) Primary phospholipase C and brain disorders. Adv Biol Regul 61:80–85. https://doi.org/10.1016/j.jbior.2015.11.003
doi: 10.1016/j.jbior.2015.11.003 pubmed: 26639088
Ratti S, Mongiorgi S, Ramazzotti G, Follo MY, Mariani GA, Suh PG et al (2017) Nuclear inositide signaling via phospholipase C. J Cell Biochem 118(8):1969–1978. https://doi.org/10.1002/jcb.25894
doi: 10.1002/jcb.25894 pubmed: 28106288
Cocco L, Follo MY, Manzoli L, Suh PG (2015) Phosphoinositide-specific phospholipase C in health and disease. J Lipid Res 56(10):1853–1860. https://doi.org/10.1194/jlr.R057984
doi: 10.1194/jlr.R057984 pubmed: 25821234 pmcid: 4583093
Martelli AM, Gilmour RS, Neri LM, Manzoli L, Corps AN, Cocco L (1991) Mitogen-stimulated events in nuclei of Swiss 3T3 cells. Evidence for a direct link between changes of inositol lipids, protein kinase C requirement and the onset of DNA synthesis. FEBS Lett. 283(2):243–246. https://doi.org/10.1016/10.1016/0014-5793(91)80598-w
doi: 10.1016/0014-5793(91)80598-w pubmed: 1646120
Lo Vasco VR (2012) Phosphoinositide pathway and the signal transduction network in neural development. Neurosci Bull 28(6):789–800. https://doi.org/10.1007/s12264-012-1283-x
doi: 10.1007/s12264-012-1283-x pubmed: 23152330 pmcid: 5561820
Spires TL, Molnár Z, Kind PC, Cordery PM, Upton AL, Blakemore C et al (2005) Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta1 signalling. Cereb Cortex 15(4):385–393. https://doi.org/10.1093/cercor/bhh141
doi: 10.1093/cercor/bhh141 pubmed: 15749982
Rusciano I, Marvi MV, Owusu Obeng E, Mongiorgi S, Ramazzotti G, Follo MY et al (2021) Location-dependent role of phospholipase C signaling in the brain: physiology and pathology. Adv Biol Regul 79:100771. https://doi.org/10.1016/j.jbior.2020.100771
doi: 10.1016/j.jbior.2020.100771 pubmed: 33303387
García del Caño G, Montaña M, Aretxabala X, González-Burguera I, López de Jesús M, Barrondo S et al (2014) Nuclear phospholipase C-β1 and diacylglycerol LIPASE-α in brain cortical neurons. Adv Biol Regul 54:12–23. https://doi.org/10.1016/j.jbior.2013.09.003
doi: 10.1016/j.jbior.2013.09.003 pubmed: 24076015
Kim D, Jun KS, Lee SB, Kang NG, Min DS, Kim YH et al (1997) Phospholipase C isozymes selectively couple to specific neurotransmitter receptors. Nature 389(6648):290–293. https://doi.org/10.1038/38508
doi: 10.1038/38508 pubmed: 9305844
Poduri A, Chopra SS, Neilan EG, Elhosary PC, Kurian MA, Meyer E et al (2012) Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy. Epilepsia 53(8):e146–e150. https://doi.org/10.1111/j.1528-1167.2012.03538.x
doi: 10.1111/j.1528-1167.2012.03538.x pubmed: 22690784
Kao CF, Jia P, Zhao Z, Kuo PH (2012) Enriched pathways for major depressive disorder identified from a genome-wide association study. Int J Neuropsychopharmacol 15(10):1401–1411. https://doi.org/10.1017/S1461145711001891
doi: 10.1017/S1461145711001891 pubmed: 22243633
Lo Vasco VR, Cardinale G, Polonia P (2012) Deletion of PLCB1 gene in schizophrenia-affected patients. J Cell Mol Med 16(4):844–851. https://doi.org/10.1111/j.1582-4934.2011.01363.x
doi: 10.1111/j.1582-4934.2011.01363.x pubmed: 22507702
Chen X, Hao A, Li X, Ye K, Zhao C, Yang H et al (2020) Activation of JNK and p38 MAPK Mediated by ZDHHC17 drives glioblastoma multiforme development and malignant progression. Theranostics 10(3):998–1015. https://doi.org/10.7150/thno.40076
doi: 10.7150/thno.40076 pubmed: 31938047 pmcid: 6956818
Udawela M, Scarr E, Hannan AJ, Thomas EA, Dean B (2011) Phospholipase C beta 1 expression in the dorsolateral prefrontal cortex from patients with schizophrenia at different stages of illness. Aust N Z J Psychiatry 45(2):140–147. https://doi.org/10.3109/00048674.2010.533364
doi: 10.3109/00048674.2010.533364 pubmed: 21091263
Martelli AM, Faenza I, Billi AM, Manzoli L, Evangelisti C, Falà F et al (2006) Intranuclear 3’-phosphoinositide metabolism and Akt signaling: new mechanisms for tumorigenesis and protection against apoptosis? Cell Signal 18(8):1101–1107. https://doi.org/10.1016/j.cellsig.2006.01.011
doi: 10.1016/j.cellsig.2006.01.011 pubmed: 16516442
Ramos AR, Elong Edimo W, Erneux C (2018) Phosphoinositide 5-phosphatase activities control cell motility in glioblastoma: two phosphoinositides PI(4,5)P2 and PI(3,4)P2 are involved. Adv Biol Regul 67:40–48. https://doi.org/10.1016/j.jbior.2017.09.001
doi: 10.1016/j.jbior.2017.09.001 pubmed: 28916189
Marvi MV, Mongiorgi S, Ramazzotti G, Follo MY, Billi AM, Zoli M et al (2021) Role of PLCγ1 in the modulation of cell migration and cell invasion in glioblastoma. Adv Biol Regul. https://doi.org/10.1016/j.jbior.2021.100838
doi: 10.1016/j.jbior.2021.100838 pubmed: 34819252
Lu G, Chang JT, Liu Z, Chen Y, Li M, Zhu JJ (2016) Phospholipase C beta 1: a candidate signature gene for proneural subtype high-grade glioma. Mol Neurobiol 53(9):6511–6525. https://doi.org/10.1007/s12035-015-9518-2
doi: 10.1007/s12035-015-9518-2 pubmed: 26614510
Sengelaub CA, Navrazhina K, Ross JB, Halberg N, Tavazoie SF (2016) PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling. EMBO J 35(1):62–76. https://doi.org/10.15252/embj.201591973
doi: 10.15252/embj.201591973 pubmed: 26620550
Audhya A, Emr SD (2003) Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J 22(16):4223–4236. https://doi.org/10.1093/emboj/cdg397
doi: 10.1093/emboj/cdg397 pubmed: 12912920 pmcid: 175787
Mongiorgi S, Follo MY, Yang YR, Ratti S, Manzoli L, McCubrey JA et al (2016) Selective activation of nuclear PI-PLCbeta1 during normal and therapy-related differentiation. Curr Pharm Des 22(16):2345–2348. https://doi.org/10.2174/1381612822666160226132338
doi: 10.2174/1381612822666160226132338 pubmed: 26916022
Manzoli L, Mongiorgi S, Clissa C, Finelli C, Billi AM, Poli A et al (2014) Strategic role of nuclear inositide signalling in myelodysplastic syndromes therapy. Mini Rev Med Chem 14(11):873–883
doi: 10.2174/1389557514666141013125936
Shankar A, Kumar S, Iskander AS, Varma NR, Janic B, deCarvalho A et al (2014) Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo. Chin J Cancer 33(3):148–158. https://doi.org/10.5732/cjc.013.10095
doi: 10.5732/cjc.013.10095 pubmed: 24016393 pmcid: 3966215
Iwadate Y (2016) Epithelial-mesenchymal transition in glioblastoma progression. Oncol Lett 11(3):1615–1620. https://doi.org/10.3892/ol.2016.4113
doi: 10.3892/ol.2016.4113 pubmed: 26998052 pmcid: 4774466
Medici D, Hay ED, Olsen BR (2008) Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell 19(11):4875–4887. https://doi.org/10.1091/mbc.e08-05-0506
doi: 10.1091/mbc.e08-05-0506 pubmed: 18799618 pmcid: 2575183
Gladson CL (1999) The extracellular matrix of gliomas: modulation of cell function. J Neuropathol Exp Neurol 58(10):1029–1040. https://doi.org/10.1097/00005072-199910000-00001
doi: 10.1097/00005072-199910000-00001 pubmed: 10515226
Wang M, Wang T, Liu S, Yoshida D, Teramoto A (2003) The expression of matrix metalloproteinase-2 and -9 in human gliomas of different pathological grades. Brain Tumor Pathol 20(2):65–72. https://doi.org/10.1007/BF02483449
doi: 10.1007/BF02483449 pubmed: 14756443
Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H et al (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79(11–12):1828–1835. https://doi.org/10.1038/sj.bjc.6690291
doi: 10.1038/sj.bjc.6690291 pubmed: 10206300 pmcid: 2362801
Nager M, Bhardwaj D, Cantí C, Medina L, Nogués P, Herreros J (2012) β-Catenin signalling in glioblastoma multiforme and glioma-initiating cells. Chemother Res Pract 2012:192362. https://doi.org/10.1155/2012/192362
doi: 10.1155/2012/192362 pubmed: 22400111 pmcid: 3286890
Mehta S, Lo CC (2018) Developmentally regulated signaling pathways in glioma invasion. Cell Mol Life Sci 75(3):385–402. https://doi.org/10.1007/s00018-017-2608-8
doi: 10.1007/s00018-017-2608-8 pubmed: 28821904
Ramaswamy P, Nanjaiah ND, Borkotokey M (2019) Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: possible implication on migration and proliferation. Ann Neurosci 26(2):52–56. https://doi.org/10.5214/ans.0972.7531.260203
doi: 10.5214/ans.0972.7531.260203 pubmed: 31975773 pmcid: 6894623
Park J, Lee W, Yun S, Kim SP, Kim KH, Kim JI et al (2020) STAT3 is a key molecule in the oncogenic behavior of diffuse intrinsic pontine glioma. Oncol Lett 20(2):1989–1998. https://doi.org/10.3892/ol.2020.11699
doi: 10.3892/ol.2020.11699 pubmed: 32724445 pmcid: 7377111
Louis DN, Wesseling P, Aldape K, Brat DJ, Capper D, Cree IA et al (2020) cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol 30(4):844–856. https://doi.org/10.1111/bpa.12832
doi: 10.1111/bpa.12832 pubmed: 32307792 pmcid: 8018152
Gabusi A, Gissi DB, Montebugnoli L, Asioli S, Tarsitano A, Marchetti C et al (2020) Prognostic impact of intra-field heterogeneity in oral squamous cell carcinoma. Virchows Arch 476(4):585–595. https://doi.org/10.1007/s00428-019-02656-z
doi: 10.1007/s00428-019-02656-z pubmed: 31468114
Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, Cech M et al (2018) The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res 46(W1):W537–W544. https://doi.org/10.1093/nar/gky379
doi: 10.1093/nar/gky379 pubmed: 29790989 pmcid: 6030816
Tresch NS, Fuchs D, Morandi L, Tonon C, Rohrer Bley C, Nytko KJ (2021) Temozolomide is additive with cytotoxic effect of irradiation in canine glioma cell lines. Vet Med Sci. https://doi.org/10.1002/vms3.620
doi: 10.1002/vms3.620 pubmed: 34477324 pmcid: 8604143
Krainer J, Weinhäusel A, Hanak K, Pulverer W, Özen S, Vierlinger K et al (2019) EPIC-TABSAT: analysis tool for targeted bisulfite sequencing experiments and array-based methylation studies. Nucleic Acids Res 47(W1):W166–W170. https://doi.org/10.1093/nar/gkz398
doi: 10.1093/nar/gkz398 pubmed: 31106358 pmcid: 6602470
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D et al (2021) The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol 23(8):1231–1251. https://doi.org/10.1093/neuonc/noab106
doi: 10.1093/neuonc/noab106 pubmed: 34185076 pmcid: 8328013
Liu CA, Chang CY, Hsueh KW, Su HL, Chiou TW, Lin SZ et al (2018) Migration/invasion of malignant gliomas and implications for therapeutic treatment. Int J Mol Sci 19(4):1115. https://doi.org/10.3390/ijms19041115
doi: 10.3390/ijms19041115 pmcid: 5979613
Owusu Obeng E, Rusciano I, Marvi MV, Fazio A, Ratti S, Follo MY et al (2020) Phosphoinositide-dependent signaling in cancer: a focus on phospholipase C isozymes. Int J Mol Sci 21(7):2581. https://doi.org/10.3390/ijms21072581
doi: 10.3390/ijms21072581 pmcid: 7177890
Ratti S, Follo MY, Ramazzotti G, Faenza I, Fiume R, Suh PG et al (2019) Nuclear phospholipase C isoenzyme imbalance leads to pathologies in brain, hematologic, neuromuscular, and fertility disorders. J Lipid Res 60(2):312–317. https://doi.org/10.1194/jlr.R089763
doi: 10.1194/jlr.R089763 pubmed: 30287524
Piperigkou Z, Kyriakopoulou K, Koutsakis C, Mastronikolis S, Karamanos NK (2021) Key matrix remodeling enzymes: functions and targeting in cancer. Cancers (Basel). 13(6):1441. https://doi.org/10.3390/cancers13061441
doi: 10.3390/cancers13061441 pubmed: 33809973 pmcid: 8005147
Jin Q, Zhang W, Qiu XG, Yan W, You G, Liu YW et al (2011) Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma. Chin Med J (Engl) 124(17):2584–2588
Saini KS, Loi S, de Azambuja E, Metzger-Filho O, Saini ML, Ignatiadis M et al (2013) Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev 39(8):935–946. https://doi.org/10.1016/j.ctrv.2013.03.009
doi: 10.1016/j.ctrv.2013.03.009 pubmed: 23643661
Ji H, Wang J, Nika H, Hawke D, Keezer S, Ge Q et al (2009) EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin. Mol Cell 36(4):547–559. https://doi.org/10.1016/j.molcel.2009.09.034
doi: 10.1016/j.molcel.2009.09.034 pubmed: 19941816 pmcid: 2784926
Zolezzi JM, Santos MJ, Bastías-Candia S, Pinto C, Godoy JA, Inestrosa NC (2017) PPARs in the central nervous system: roles in neurodegeneration and neuroinflammation. Biol Rev Camb Philos Soc 92(4):2046–2069. https://doi.org/10.1111/brv.12320
doi: 10.1111/brv.12320 pubmed: 28220655
Vallée A, Lecarpentier Y (2018) Crosstalk between peroxisome proliferator-activated receptor gamma and the canonical WNT/β-Catenin pathway in chronic inflammation and oxidative stress during carcinogenesis. Front Immunol 9:745. https://doi.org/10.3389/fimmu.2018.00745
doi: 10.3389/fimmu.2018.00745 pubmed: 29706964 pmcid: 5908886
Fiume R, Ramazzotti G, Faenza I, Piazzi M, Bavelloni A, Billi AM et al (2012) Nuclear PLCs affect insulin secretion by targeting PPARγ in pancreatic β cells. FASEB J 26(1):203–210. https://doi.org/10.1096/fj.11-186510
doi: 10.1096/fj.11-186510 pubmed: 21974932
Xie B, Zhang L, Hu W, Fan M, Jiang N, Duan Y et al (2019) Dual blockage of STAT3 and ERK1/2 eliminates radioresistant GBM cells. Redox Biol 24:101189. https://doi.org/10.1016/j.redox.2019.101189
doi: 10.1016/j.redox.2019.101189 pubmed: 30986607 pmcid: 6463934

Auteurs

Stefano Ratti (S)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Maria Vittoria Marvi (MV)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Sara Mongiorgi (S)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Eric Owusu Obeng (EO)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Isabella Rusciano (I)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Giulia Ramazzotti (G)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy.

Luca Morandi (L)

Functional and Molecular Neuroimaging Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126, Bologna, Italy.

Sofia Asioli (S)

Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126, Bologna, Italy.
Anatomic Pathology Unit, Azienda USL Di Bologna, 40124, Bologna, Italy.
Pituitary Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.

Matteo Zoli (M)

Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126, Bologna, Italy.
Pituitary Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.

Diego Mazzatenta (D)

Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126, Bologna, Italy.
Pituitary Unit, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, 40139, Bologna, Italy.

Pann-Ghill Suh (PG)

Korea Brain Research Institute, Daegu, 41062, Korea.
School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea.

Lucia Manzoli (L)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy. lucia.manzoli@unibo.it.

Lucio Cocco (L)

Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126, Bologna, Italy. lucio.cocco@unibo.it.

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