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Brain Tumor Pathology
Published in: Brain Tumor Pathology 2/2019

01-04-2019 | Glioblastoma | Review Article

Novel concept of the border niche: glioblastoma cells use oligodendrocytes progenitor cells (GAOs) and microglia to acquire stem cell-like features

Authors: Takuichiro Hide, Ichiyo Shibahara, Toshihiro Kumabe

Published in: Brain Tumor Pathology | Issue 2/2019

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Abstract

Glioblastoma (GBM) is a major malignant brain tumor developing in adult brain white matter, characterized by rapid growth and invasion. GBM cells spread into the contralateral hemisphere, even during early tumor development. However, after complete resection of tumor mass, GBM commonly recurs around the tumor removal cavity, suggesting that a microenvironment at the tumor border provides chemo-radioresistance to GBM cells. Thus, clarification of the tumor border microenvironment is critical for improving prognosis in GBM patients. MicroRNA (miRNA) expression in samples from the tumor, tumor border, and peripheral region far from tumor mass was compared, and five miRNAs showing characteristically higher expression in the tumor border were identified, with the top three related to oligodendrocyte differentiation. Pathologically, oligodendrocyte lineage cells increased in the border, but were rare in tumors. Macrophages/microglia also colocalized in the border area. Medium cultured with oligodendrocyte progenitor cells (OPCs) and macrophages induced stemness and chemo-radioresistance in GBM cells, suggesting that OPCs and macrophages/microglia constitute a special microenvironment for GBM cells at the tumor border. The supportive function of OPCs for GBM cells has not been discussed previously. OPCs are indispensable for GBM cells to establish special niches for chemo-radioresistance outside the tumor mass.
Literature
1.
Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466CrossRefPubMed
2.
Ostrom QT, Gittleman H, Liao P et al (2014) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007–2011. Neuro Oncol 16(Suppl 4):iv1-63CrossRefPubMed
3.
Wilson CB (1992) Glioblastoma: the past, the present, and the future. Clin Neurosurg 38:32–48PubMed
4.
Brandes AA, Tosoni A, Franceschi E et al (2009) Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status. J Clin Oncol 27:1275–1279CrossRefPubMed
5.
Schaub C, Kebir S, Junold N et al (2018) Tumor growth patterns of MGMT-non-methylated glioblastoma in the randomized GLARIUS trial. J Cancer Res Clin Oncol 144:1581–1589CrossRefPubMed
6.
Hide T, Komohara Y, Miyasato Y et al (2018) Oligodendrocyte progenitor cells and macrophages/microglia produce glioma stem cell niches at the tumor border. EBioMedicine 30:94–104CrossRefPubMedPubMedCentral
7.
Singh SK, Hawkins C, Clarke ID et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401CrossRefPubMed
8.
Hide T, Makino K, Nakamura H et al (2013) New treatment strategies to eradicate cancer stem cells and niches in glioblastoma. Neurol Med Chir (Tokyo) 53:764–772CrossRef
9.
Charles NA, Holland EC, Gilbertson R et al (2011) The brain tumor microenvironment. Glia 59:1169–1180CrossRefPubMed
10.
Fidoamore A, Cristiano L, Antonosante A et al (2016) Glioblastoma stem cells microenvironment: the paracrine roles of the niche in drug and radioresistance. Stem Cells Int 2016:6809105CrossRefPubMedPubMedCentral
11.
Ishii A, Kimura T, Sadahiro H et al (2016) Histological characterization of the tumorigenic “Peri-Necrotic Niche” harboring quiescent stem-like tumor cells in glioblastoma. PLoS One 11:e0147366CrossRefPubMedPubMedCentral
12.
13.
Schiffer D, Annovazzi L, Casalone C et al (2018) Glioblastoma: microenvironment and niche concept. Cancers (Basel) 11(1):5CrossRef
14.
Schiffer D, Mellai M, Bovio E et al (2018) Glioblastoma niches: from the concept to the phenotypical reality. Neurol Sci 39:1161–1168CrossRefPubMed
15.
16.
17.
Leblond MM, Peres EA, Helaine C et al (2017) M2 macrophages are more resistant than M1 macrophages following radiation therapy in the context of glioblastoma. Oncotarget 8:72597–72612CrossRefPubMedPubMedCentral
18.
Arcuri C, Fioretti B, Bianchi R et al (2017) Microglia-glioma cross-talk: a two way approach to new strategies against glioma. Front Biosci (Landmark Ed) 22:268–309CrossRef
19.
Roesch S, Rapp C, Dettling S et al (2018) When immune cells turn bad-tumor-associated microglia/macrophages in glioma. Int J Mol Sci 19:436CrossRefPubMedCentral
20.
Kros JM, Mustafa DM, Dekker LJ et al (2015) Circulating glioma biomarkers. Neuro Oncol 17:343–360CrossRefPubMed
21.
Li C, Sun J, Xiang Q et al (2016) Prognostic role of microRNA-21 expression in gliomas: a meta-analysis. J Neurooncol 130:11–17CrossRefPubMed
22.
Kohlhapp FJ, Mitra AK, Lengyel E et al (2015) MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene 34:5857CrossRefPubMedPubMedCentral
23.
24.
25.
Dugas JC, Cuellar TL, Scholze A et al (2010) Dicer1 and miR-219 Are required for normal oligodendrocyte differentiation and myelination. Neuron 65:597–611CrossRefPubMedPubMedCentral
26.
27.
Nazari B, Soleimani M, Ebrahimi-Barough S et al (2018) Overexpression of miR-219 promotes differentiation of human induced pluripotent stem cells into pre-oligodendrocyte. J Chem Neuroanat 91:8–16CrossRefPubMed
28.
Wegener A, Deboux C, Bachelin C et al (2015) Gain of Olig2 function in oligodendrocyte progenitors promotes remyelination. Brain 138:120–135CrossRefPubMed
29.
Birey F, Kokkosis AG, Aguirre A (2017) Oligodendroglia-lineage cells in brain plasticity, homeostasis and psychiatric disorders. Curr Opin Neurobiol 47:93–103CrossRefPubMedPubMedCentral
30.
Lou W, Zhang X, Hu XY et al (2016) MicroRNA-219-5p inhibits morphine-induced apoptosis by targeting key cell cycle regulator WEE1. Med Sci Monit 22:1872–1879CrossRefPubMedPubMedCentral
31.
Kuratsu J, Leonard EJ, Yoshimura T (1989) Production and characterization of human glioma cell-derived monocyte chemotactic factor. J Natl Cancer Inst 81:347–351CrossRefPubMed
32.
Komohara Y, Horlad H, Ohnishi K et al (2012) Importance of direct macrophage-tumor cell interaction on progression of human glioma. Cancer Sci 103:2165–2172CrossRefPubMedPubMedCentral
33.
34.
Pyonteck SM, Akkari L, Schuhmacher AJ et al (2013) CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med 19:1264–1272CrossRefPubMedPubMedCentral
35.
36.
Komohara Y, Jinushi M, Takeya M (2014) Clinical significance of macrophage heterogeneity in human malignant tumors. Cancer Sci 105:1–8CrossRefPubMed
37.
38.
Kaneko S, Nakatani Y, Takezaki T et al (2015) Ceacam1L modulates STAT3 signaling to control the proliferation of glioblastoma-initiating cells. Cancer Res 75:4224–4234CrossRefPubMed
39.
Diksin M, Smith SJ, Rahman R (2017) The molecular and phenotypic basis of the glioma invasive perivascular niche. Int J Mol Sci 18(11):2342CrossRefPubMedCentral
40.
Calabrese C, Poppleton H, Kocak M et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69–82CrossRefPubMed
41.
Ho IAW, Shim WSN (2017) Contribution of the microenvironmental Niche to glioblastoma heterogeneity. Biomed Res Int 2017:9634172PubMedPubMedCentral
42.
43.
44.
Yeung MS, Zdunek S, Bergmann O et al (2014) Dynamics of oligodendrocyte generation and myelination in the human brain. Cell 159:766–774CrossRefPubMed
45.
46.
Hide T, Takezaki T, Nakatani Y et al (2011) Combination of a ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells. Stem Cells 29:590–599CrossRefPubMed
47.
48.
Galvao RP, Kasina A, McNeill RS et al (2014) Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process. Proc Natl Acad Sci USA 111:E4214–E4223CrossRefPubMedPubMedCentral
49.
Hughes EG, Kang SH, Fukaya M et al (2013) Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat Neurosci 16:668–676CrossRefPubMedPubMedCentral
50.
51.
Fernandez-Castaneda A, Gaultier A (2016) Adult oligodendrocyte progenitor cells—multifaceted regulators of the CNS in health and disease. Brain Behav Immun 57:1–7CrossRefPubMedPubMedCentral
52.
53.
Young KM, Psachoulia K, Tripathi RB et al (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron 77:873–885CrossRefPubMedPubMedCentral
54.
Marques S, Zeisel A, Codeluppi S et al (2016) Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system. Science 352:1326–1329CrossRefPubMedPubMedCentral
55.
Hosono J, Morikawa S, Ezaki T et al (2017) Pericytes promote abnormal tumor angiogenesis in a rat RG2 glioma model. Brain Tumor Pathol 34:120–129CrossRefPubMed
56.
Butovsky O, Ziv Y, Schwartz A et al (2006) Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31:149–160CrossRefPubMed
57.
Shigemoto-Mogami Y, Hoshikawa K, Goldman JE et al (2014) Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci 34:2231–2243CrossRefPubMedPubMedCentral
58.
Miron VE (2017) Microglia-driven regulation of oligodendrocyte lineage cells, myelination, and remyelination. J Leukoc Biol 101:1103–1108CrossRefPubMed
59.
60.
61.
Guan X, Hasan MN, Maniar S et al (2018) Reactive astrocytes in glioblastoma multiforme. Mol Neurobiol 55:6927–6938CrossRefPubMed
62.
Brandao M, Simon T, Critchley G et al (2019) Astrocytes, the rising stars of the glioblastoma microenvironment. Glia 67:779–790CrossRefPubMed
63.
Katz AM, Amankulor NM, Pitter K et al (2012) Astrocyte-specific expression patterns associated with the PDGF-induced glioma microenvironment. PLoS One 7:e32453CrossRefPubMedPubMedCentral
64.
Barcia C Jr, Gomez A, Gallego-Sanchez JM et al (2009) Infiltrating CTLs in human glioblastoma establish immunological synapses with tumorigenic cells. Am J Pathol 175:786–798CrossRefPubMedPubMedCentral
65.
Lundgaard I, Osorio MJ, Kress BT et al (2014) White matter astrocytes in health and disease. Neuroscience 276:161–173CrossRefPubMed
66.
Moore CS, Abdullah SL, Brown A et al (2011) How factors secreted from astrocytes impact myelin repair. J Neurosci Res 89:13–21CrossRefPubMed
67.
Bardehle S, Kruger M, Buggenthin F et al (2013) Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation. Nat Neurosci 16:580–586CrossRefPubMed
68.
Gibson EM, Purger D, Mount CW et al (2014) Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344:1252304CrossRefPubMedPubMedCentral
69.
Mitew S, Gobius I, Fenlon LR et al (2018) Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner. Nat Commun 9:306CrossRefPubMedPubMedCentral
70.
71.
72.
73.
74.
Muller C, Holtschmidt J, Auer M et al (2014) Hematogenous dissemination of glioblastoma multiforme. Sci Transl Med 6:247ra101CrossRefPubMed
75.
Macarthur KM, Kao GD, Chandrasekaran S et al (2014) Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay. Cancer Res 74:2152–2159CrossRefPubMedPubMedCentral
76.
Liu T, Xu H, Huang M et al (2018) Circulating glioma cells exhibit stem cell-like properties. Cancer Res 78:6632–6642PubMedPubMedCentral
77.
Muragaki Y, Akimoto J, Maruyama T et al (2013) Phase II clinical study on intraoperative photodynamic therapy with talaporfin sodium and semiconductor laser in patients with malignant brain tumors. J Neurosurg 119:845–852CrossRefPubMed
78.
Nitta M, Muragaki Y, Maruyama T et al (2018) Role of photodynamic therapy using talaporfin sodium and a semiconductor laser in patients with newly diagnosed glioblastoma. J Neurosurg 1:1–8CrossRef
79.
Westphal M, Hilt DC, Bortey E et al (2003) A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 5:79–88CrossRefPubMedPubMedCentral
80.
Shibahara I, Hanihara M, Watanabe T et al (2018) Tumor microenvironment after biodegradable BCNU wafer implantation: special consideration of immune system. J Neurooncol 137:417–427CrossRefPubMed
81.
Asano K, Kurose A, Kamataki A et al (2018) Importance and accuracy of intraoperative frozen section diagnosis of the resection margin for effective carmustine wafer implantation. Brain Tumor Pathol 35:131–140CrossRefPubMed
82.
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
83.
Zschaeck S, Wust P, Graf R et al (2018) Locally dose-escalated radiotherapy may improve intracranial local control and overall survival among patients with glioblastoma. Radiat Oncol 13:251CrossRefPubMedPubMedCentral
Metadata
Title
Novel concept of the border niche: glioblastoma cells use oligodendrocytes progenitor cells (GAOs) and microglia to acquire stem cell-like features
Authors
Takuichiro Hide
Ichiyo Shibahara
Toshihiro Kumabe
Publication date
01-04-2019
Publisher
Springer Singapore
Published in
Brain Tumor Pathology / Issue 2/2019
Print ISSN: 1433-7398
Electronic ISSN: 1861-387X
DOI
https://doi.org/10.1007/s10014-019-00341-2

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