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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 2/2016

01-06-2016 | Topic Review

Neural stem cells, the subventricular zone and radiotherapy: implications for treating glioblastoma

Authors: Andrew W. Smith, Minesh P. Mehta, A. Gabriella Wernicke

Published in: Journal of Neuro-Oncology | Issue 2/2016

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Abstract

Over the past decade, advances in neuroscience have suggested that neural stem cells resident in specific regions of the adult brain may be involved in development of both primary and recurrent glioblastoma. Neurogenesis and malignant transformation occurs in the subventricular zone adjacent to the lateral ventricles. This region holds promise as a potential target for therapeutic intervention with radiotherapy. However, irradiation of a larger brain volume is not without risk, and significant side effects have been observed. The current literature remains contradictory regarding the efficacy of deliberate intervention with radiation to the subventricular zone. This critical review discusses the connection between neural stem cells and development of glioblastoma, explores the behavior of tumors associated with the subventricular zone, summarizes the discordant literature with respect to the effects of irradiation, and reviews other targeted therapies to this intriguing region.
Literature
1.
Sanai N, Tramontin AD, Quinones-Hinjosa A et al (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744CrossRefPubMed
2.
Eriksson PS, Perfilieva E, Bjork-Eriksson T et al (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317CrossRefPubMed
3.
Nunes MC, Roy NS, Keyoung HM et al (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9:439–447CrossRefPubMed
4.
Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. New Engl J Med 353:811–822CrossRefPubMed
5.
Barani IJ, Benedict SH, Lin PS (2007) Neural stem cells: implications for the conventional radiotherapy of central nervous system malignancies. Int J Radiat Oncol Biol Phys 68:324–333CrossRefPubMed
6.
Kut C, Redmond KJ (2014) New considerations in radiation treatment planning for brain tumors: neural progenitor cell-containing niches. Semin Radiat Oncol 24:265–272CrossRefPubMedPubMedCentral
7.
8.
Zhang RL, Zhang ZG, Chopp M (2005) Neurogenesis in the adult ischemic brain: generation, migration, survival, and restorative therapy. Neuroscientist 11:408–416CrossRefPubMed
9.
Goings GE, Sahni V, Szele FG (2004) Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res 996:213–226CrossRefPubMed
10.
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494CrossRefPubMed
11.
Shen Q, Goderie SK, Jin L et al (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304:1338–1340CrossRefPubMed
12.
Machold R, Hayashi S, Rutlin M et al (2003) Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 39:937–950CrossRefPubMed
13.
Dahmane N, Sanchez P, Gitton Y et al (2001) The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128:5201–5212PubMed
14.
15.
Caporaso GL, Lim DA, Alvarez-Buylla A et al (2003) Telomerase activity in the subventricular zone of adult mice. Mol Cell Neurosci 23:693–702CrossRefPubMed
16.
Sundar SJ, Hsieh JK, Manjila S et al (2014) The role of cancer stem cells in glioblastoma. Neurosurg Focus 37:E6CrossRefPubMed
17.
Ignatova TN, Kukekov VG, Laywell ED et al (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39:193–206CrossRefPubMed
18.
Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401CrossRefPubMed
19.
Bao S, Wu Q, McLendon RE et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760CrossRefPubMed
20.
21.
Jackson EL, Garcia-Verdugo JM, Gil-Perotin S et al (2006) PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling. Neuron 51:187–199CrossRefPubMed
22.
Gonzalez-Perez O, Quinones-Hinojosa A (2010) Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes. Glia 58:975–983PubMedPubMedCentral
23.
Lim DA, Cha S, Mayo MC et al (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9:424–429CrossRefPubMedPubMedCentral
24.
Jafri NF, Clarke JL, Weinberg V et al (2013) Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol 15:91–96CrossRefPubMedPubMedCentral
25.
Sonoda Y, Saito R, Kanamori M et al (2014) The association of subventricular zone involvement at recurrence with survival after repeat surgery in patients with recurrent glioblastoma. Neurol Med Chir 54:302–309CrossRef
26.
Adeberg S, Bostel T, Konig L et al (2014) A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival? Radiat Oncol 9:95CrossRefPubMedPubMedCentral
27.
Young GS, Macklin EA, Setayesh K et al (2011) Longitudinal MRI evidence for decreased survival among periventricular glioblastoma. J Neurooncol 104:261–269CrossRefPubMedPubMedCentral
28.
Adeberg S, Konig L, Bostel T et al (2014) Glioblastoma recurrence patterns after radiation therapy with regard to the subventricular zone. Int J Radiat Oncol Biol Phys 90:886–893CrossRefPubMed
29.
30.
Gupta T, Nair V, Jalali R (2014) Stem cell niche irradiation in glioblastoma: providing a ray of hope? CNS Oncol 3(5):367–376CrossRefPubMed
31.
Corn BW, Raizer J, Kanner AA (2014) Should the subventricular zone be part of the “rad” zone? J Neurooncol 118:423–424CrossRefPubMed
32.
Sharma A, Munshi A, Mohanti BK et al (2013) Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis. In regard to Lee et al. Int J Radiat Oncol Biol Phys 87:631CrossRefPubMed
33.
Gibbs IC, Haas-Kogan D, Terezakis S et al (2013) The subventricular zone neural progenitor cell hypothesis in glioblastoma: epiphany, trojan horse, or cheshire fact? Int J Radiat Oncol Biol Phys 86:606–608CrossRefPubMed
34.
Chera BS, Amdur RJ, Patel P et al (2009) A radiation oncologist’s guide to contouring the hippocampus. Am J Clin Oncol 32:20–22CrossRefPubMed
35.
Evers P, Lee PP, DeMarco J et al (2010) Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma. BMC Cancer 10:384CrossRefPubMedPubMedCentral
36.
Gupta T, Nair V, Paul SN et al (2012) Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma? J Neurooncol 109:195–203CrossRefPubMed
37.
Lee P, Eppinga W, Lagerwaard F et al (2013) Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis. Int J Radiat Oncol Biol Phys 86:609–615CrossRefPubMed
38.
Chen L, Guerrero-Cazares H, Ye X et al (2013) Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys 86:616–622CrossRefPubMedPubMedCentral
39.
Iuchi T, Hatano K, Kodama T et al (2014) Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys 88:793–800CrossRefPubMed
40.
Ravind RR, Prameela CG, Dinesh M (2015) P011 Sub-ventricular zone irradiation in glioblastoma: can it increase survival? Eur J Cancer 51(suppl 2):e23CrossRef
41.
Slotman BJE, Eppinga WSC, de Haan PF et al (2011) Is irradiation of potential cancer stem cell niches in the subventricular zones indicated in GBM? (abstr 1058). Int J Radiat Oncol Biol Phys 81(Suppl 1):184CrossRef
42.
Elicin O, Inac E, Uzel EK et al (2014) Relationship between survival and increased radiation dose to subventricular zone in glioblastoma is controversial. J Neurooncol 118:413–419CrossRefPubMed
43.
Chua M, Kusumawidjaja G, Gan P et al (2014) Dose-escalated intensity modulated radiotherapy (IMRT) and increased radiation doses to subventricular zones (SVZ) in treatment outcomes of patients with glioblastoma (GBM). J Clin Oncol 32:e13031
44.
Tu SM, Lin SH, Logothetis CJ (2002) Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol 3:508–513CrossRefPubMed
45.
Molenaar RJ, Verbaan D, Lamba S et al (2014) The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro Oncol 16:1263–1273CrossRefPubMedPubMedCentral
46.
Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomized controlled trial. Lancet Oncol 10:1037–1044CrossRefPubMed
47.
Grill J, Renaux VK, Bulteau C et al (1999) Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes. Int J Radiat Oncol Biol Phys 45:137–145CrossRefPubMed
48.
Surma-aho O, Niemela M, Vilkki J et al (2001) Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients. Neurology 56:1285–1290CrossRefPubMed
49.
Mulhern RK, Merchant TE, Gajjar A et al (2004) Late neurocognitive sequelae in survivors of brain tumours in childhood. Lancet Oncol 5:399–408CrossRefPubMed
50.
Prust MJ, Jafari-Khouzani K, Kalpathy-Cramer J et al (2015) Standard chemoradiation for glioblastoma results in progressive brain volume loss. Neurology 85(8):683–691CrossRefPubMed
51.
Claude L, Perol D, Ray-Coquard I et al (2005) Lymphopenia: a new independent prognostic factor for survival in patients treated with whole brain radiotherapy for brain metastases from breast carcinoma. Radiother Oncol 76:334–339CrossRefPubMed
52.
Grossman SA, Ye X, Lesser G et al (2011) Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 17:5473–5480CrossRefPubMedPubMedCentral
53.
MacLennan IC, Kay HE (1978) Analysis of treatment in childhood leukemia. IV. The critical association between dose fractionation and immunosuppression induced by cranial irradiation. Cancer 41:108–111CrossRefPubMed
54.
Ellsworth S, Balmanoukian A, Kos F et al (2014) Sustained CD4 T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide. Oncoimmunology 3:e27357CrossRefPubMedPubMedCentral
55.
Yovino S, Grossman SA (2012) Severity, etiology and possible consequences of treatment-related lymphopenia in patients with newly diagnosed high-grade gliomas. CNS Oncol 1:149–154CrossRefPubMedPubMedCentral
56.
57.
Huang J, DeWees TA, Badiyan SN et al (2015) Clinical and dosimetric predictors of acute severe lymphopenia during radiation therapy and concurrent temozolomide for high-grade glioma. Int J Radiat Oncol Biol Phys 92:1000–1007CrossRefPubMed
58.
Redmond KJ, Mahone EM, Horska A (2013) Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study. Neuro Oncol 15:1455CrossRefPubMedPubMedCentral
59.
Lao CL, Lu CS, Chen JC (2013) Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type-b and -c cells in adult subventricular zone. Glia 61:475–489CrossRefPubMed
60.
Yang P, Arnold SA, Habas A et al (2008) Ciliary neurotrophic factor mediates dopamine D2 receptor-induced CNS neurogenesis in adult mice. J Neurosci 28:2231–2241CrossRefPubMed
61.
Merlo S, Canonico PL, Sortino MA (2011) Distinct effects of pramipexole on the proliferation of adult mouse sub-ventricular zone-derived cells and the appearance of a neuronal phenotype. Neuropharmacology 60:892–900CrossRefPubMed
62.
Coronas V, Bantubungi K, Fombonne J et al (2004) Dopamine D3 receptor stimulation promotes the proliferation of cells derived from the post-natal subventricular zone. J Neurochem 91:1292–1301CrossRefPubMed
63.
Kast RE, Ellingson BM, Marosi C et al (2014) Glioblastoma treatment using perphenazine to block the subventricular zone’s tumor trophic functions. J Neurooncol 116:207–212CrossRefPubMed
64.
Cheng HW, Liang YH, Chuu CP et al (2015) Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data. Cell Death Dis 6:e1753CrossRefPubMedPubMedCentral
65.
Belcaid Z, Phallen JA, Zeng J et al (2014) Focal radiation therapy combined with 4-1bb activation and ctla-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model. PLoS One 9:e101764CrossRefPubMedPubMedCentral
66.
Zeng J, See AP, Phallen J et al (2013) Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys 86:343–349CrossRefPubMedPubMedCentral
67.
Xu Q, Liu G, Yuan X et al (2009) Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells 27:1734–1740CrossRefPubMed
68.
Allhenn D, Boushehri MA, Lamprecht A (2012) Drug delivery strategies for the treatment of malignant gliomas. Int J Pharm 436:299–310CrossRefPubMed
69.
Gilbertson RJ, Rich JN (2007) Making a tumour’s bed: glioblastoma stem cells and the vascular niche. Nat Rev Cancer 7:733–736CrossRefPubMed
Metadata
Title
Neural stem cells, the subventricular zone and radiotherapy: implications for treating glioblastoma
Authors
Andrew W. Smith
Minesh P. Mehta
A. Gabriella Wernicke
Publication date
01-06-2016
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2123-z

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