3D bioprinting; brain organoids; cell cultures of glioma cells; glioma stem cells; mouse models of glioblastoma; Oncology; Cancer Research
Abstract :
[en] Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease.
Gómez Oliva, Ricardo ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Domínguez-García, Samuel; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Carrascal, Livia; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
Abalos-Martínez, Jessica; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain
Pardillo-Díaz, Ricardo; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Verástegui, Cristina; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain
Castro, Carmen; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Nunez-Abades, Pedro; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
Geribaldi-Doldán, Noelia; Departamento de Anatomía y Embriología Humanas, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain
Language :
English
Title :
Evolution of Experimental Models in the Study of Glioblastoma: Toward Finding Efficient Treatments.
MICINN - Ministerio de Ciencia, Innovación y Universidades
Funding text :
This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (Grant Numbers RTI2018–099908-B-C21) and co-financed by the 2014-2020 ERDF Operational Programme and by the Department of Economy, Knowledge, Business and University of the Regional Government of Andalusia. Project reference: FEDER-UCA18-106647. This work has been co-financed by the Integrated Territorial Investment Operational Programme of the European Commission and by the Department of Department of Health and Families (Consejería de Salud y Familias) of the Regional Government of Andalusia. Project reference: ITI-0042-2019 ITI CÁDIZ 2019.
Goodenberger ML, Jenkins RB. Genetics of adult glioma. Cancer Genet (2012) 205(12):613–21. doi: 10.1016/j.cancergen.2012.10.009
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. Neuro Oncol (2019) 21(Suppl 5):v1–v100. doi: 10.1093/neuonc/noz150
Tan AC, Ashley DM, Lopez GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: State of the art and future directions. CA Cancer J Clin (2020) 70(4):299–312. doi: 10.3322/caac.21613
Johnson DR, O’Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. J Neurooncol (2012) 107(2):359–64. doi: 10.1007/s11060-011-0749-4
Koshy M, Villano JL, Dolecek TA, Howard A, Mahmood U, Chmura SJ, et al. Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol (2012) 107(1):207–12. doi: 10.1007/s11060-011-0738-7
Ostrom QT, Cote DJ, Ascha M, Kruchko C, Barnholtz-Sloan JS. Adult Glioma Incidence and Survival by Race or Ethnicity in the United States From 2000 to 2014. JAMA Oncol (2018) 4(9):1254–62. doi: 10.1001/jamaoncol.2018.1789
Leece R, Xu J, Ostrom QT, Chen Y, Kruchko C, Barnholtz-Sloan JS. Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007. Neuro Oncol (2017) 19(11):1553–64. doi: 10.1093/neuonc/nox091
Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin (2007) 25(4):867–90, vii. doi: 10.1016/j.ncl.2007.07.002
Linos E, Raine T, Alonso A, Michaud D. Atopy and risk of brain tumors: a meta-analysis. J Natl Cancer Inst (2007) 99(20):1544–50. doi: 10.1093/jnci/djm170
Amirian ES, Zhou R, Wrensch MR, Olson SH, Scheurer ME, Il’yasova D, et al. Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study. Cancer Epidemiol Biomarkers Prev (2016) 25(2):282–90. doi: 10.1158/1055-9965.EPI-15-0847
Scheurer ME, Etzel CJ, Liu M, Barnholtz-Sloan J, Wiklund F, Tavelin B, et al. Familial aggregation of glioma: a pooled analysis. Am J Epidemiol (2010) 172(10):1099–107. doi: 10.1093/aje/kwq261
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol (2016) 131(6):803–20. doi: 10.1007/s00401-016-1545-1
Kleinschmidt-DeMasters BK, Aisner DL, Birks DK, Foreman NK. Epithelioid GBMs show a high percentage of BRAF V600E mutation. Am J Surg Pathol (2013) 37(5):685–98. doi: 10.1097/PAS.0b013e31827f9c5e
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell (2010) 17(1):98–110. doi: 10.1016/j.ccr.2009.12.020
Zhang L, Liu Z, Li J, Huang T, Wang Y, Chang L, et al. Genomic analysis of primary and recurrent gliomas reveals clinical outcome related molecular features. Sci Rep (2019) 9(1):16058. doi: 10.1038/s41598-019-52515-9
Davis ME. Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs (2016) 20(5 Suppl):S2–8. doi: 10.1188/16.CJON.S1.2-8
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med (2005) 352(10):987–96. doi: 10.1056/NEJMoa043330
Young RM, Jamshidi A, Davis G, Sherman JH. Current trends in the surgical management and treatment of adult glioblastoma. Ann Transl Med (2015) 3(9):121. doi: 10.3978/j.issn.2305-5839.2015.05.10
Simpson L, Galanis E. Recurrent glioblastoma multiforme: advances in treatment and promising drug candidates. Expert Rev Anticancer Ther (2006) 6(11):1593–607. doi: 10.1586/14737140.6.11.1593
Zhao S, Wu J, Wang C, Liu H, Dong X, Shi C, et al. Intraoperative fluorescence-guided resection of high-grade malignant gliomas using 5-aminolevulinic acid-induced porphyrins: a systematic review and meta-analysis of prospective studies. PLoS One (2013) 8(5):e63682. doi: 10.1371/journal.pone.0063682
Garzon-Muvdi T, Kut C, Li X, Chaichana KL. Intraoperative imaging techniques for glioma surgery. Future Oncol (2017) 13(19):1731–45. doi: 10.2217/fon-2017-0092
Lau D, Magill ST, Aghi MK. Molecularly targeted therapies for recurrent glioblastoma: current and future targets. Neurosurg Focus (2014) 37(6):E15. doi: 10.3171/2014.9.FOCUS14519
Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, et al. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature (2012) 488(7412):522–6. doi: 10.1038/nature11287
Bao S, Wu Q, McLendon RE, Hao Y, 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. doi: 10.1038/nature05236
Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN. Cancer stem cells in glioblastoma. Genes Dev (2015) 29(12):1203–17. doi: 10.1101/gad.261982.115
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res (2003) 63(18):5821–8.
Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res (2007) 67(9):4010–5. doi: 10.1158/0008-5472.CAN-06-4180
Neradil J, Veselska R. Nestin as a marker of cancer stem cells. Cancer Sci (2015) 106(7):803–11. doi: 10.1111/cas.12691
Strojnik T, Rosland GV, Sakariassen PO, Kavalar R, Lah T. Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg Neurol (2007) 68(2):133–43; discussion 43-4. doi: 10.1016/j.surneu.2006.10.050
Capela A, Temple S. LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Dev Biol (2006) 291(2):300–13. doi: 10.1016/j.ydbio.2005.12.030
Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, Fontebasso AM, et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carrying IDH1/IDH2 and TP53 mutations. Acta Neuropathol (2012) 124(5):615–25. doi: 10.1007/s00401-012-1031-3
Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN. The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle (2009) 8(20):3274–84. doi: 10.4161/cc.8.20.9701
Piccirillo SG, Spiteri I, Sottoriva A, Touloumis A, Ber S, Price SJ, et al. Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. Cancer Res (2015) 75(1):194–202. doi: 10.1158/0008-5472.CAN-13-3131
Piccirillo SG, Sottoriva A, Watts C. The role of sub-ventricular zone in gliomagenesis. Aging (Albany NY) (2015) 7(10):738–9. doi: 10.18632/aging.100823
Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, et al. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature (2018) 560(7717):243–7. doi: 10.1038/s41586-018-0389-3
Charles N, Holland EC. The perivascular niche microenvironment in brain tumor progression. Cell Cycle (2010) 9(15):3012–21. doi: 10.4161/cc.9.15.12710
Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell (2010) 7(2):150–61. doi: 10.1016/j.stem.2010.07.007
Folkins C, Shaked Y, Man S, Tang T, Lee CR, Zhu Z, et al. Glioma tumor stem-like cells promote tumor angiogenesis and vasculogenesis via vascular endothelial growth factor and stromal-derived factor 1. Cancer Res (2009) 69(18):7243–51. doi: 10.1158/0008-5472.CAN-09-0167
Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, et al. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature (2004) 427(6976):740–4. doi: 10.1038/nature02301
Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, et al. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol (2006) 494(3):415–34. doi: 10.1002/cne.20798
Robertson FL, Marques-Torrejon MA, Morrison GM, Pollard SM. Experimental models and tools to tackle glioblastoma. Dis Model Mech (2019) 12(9). doi: 10.1242/dmm.040386
Fields KL, Gosling C, Megson M, Stern PL. New cell surface antigens in rat defined by tumors of the nervous system. Proc Natl Acad Sci U S A (1975) 72(4):1296–300. doi: 10.1073/pnas.72.4.1296
Sundarraj N, Schachner M, Pfeiffer SE. Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1). Proc Natl Acad Sci U S A (1975) 72(5):1927–31. doi: 10.1073/pnas.72.5.1927
de Ridder LI, Laerum OD, Mork SJ, Bigner DD. Invasiveness of human glioma cell lines in vitro: relation to tumorigenicity in athymic mice. Acta Neuropathol (1987) 72(3):207–13. doi: 10.1007/BF00691091
Notarangelo A, Trombetta D, D’Angelo V, Parrella P, Palumbo O, Storlazzi CT, et al. Establishment and genetic characterization of ANGM-CSS, a novel, immortal cell line derived from a human glioblastoma multiforme. Int J Oncol (2014) 44(3):717–24. doi: 10.3892/ijo.2013.2224
Weeber F, Ooft SN, Dijkstra KK, Voest EE. Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery. Cell Chem Biol (2017) 24(9):1092–100. doi: 10.1016/j.chembiol.2017.06.012
Torsvik A, Stieber D, Enger PO, Golebiewska A, Molven A, Svendsen A, et al. U-251 revisited: genetic drift and phenotypic consequences of long-term cultures of glioblastoma cells. Cancer Med (2014) 3(4):812–24. doi: 10.1002/cam4.219
Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: Good news and bad news. Sci Trans Med (2016) 8(354):354re3. doi: 10.1126/scitranslmed.aaf6853
Sottoriva A, Spiteri I, Piccirillo SG, Touloumis A, Collins VP, Marioni JC, et al. Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci U S A (2013) 110(10):4009–14. doi: 10.1073/pnas.1219747110
Jiang J, Qiu J, Li Q, Shi Z. Prostaglandin E2 Signaling: Alternative Target for Glioblastoma? Trends Cancer (2017) 3(2):75–8. doi: 10.1016/j.trecan.2016.12.002
Linkous A, Balamatsias D, Snuderl M, Edwards L, Miyaguchi K, Milner T, et al. Modeling Patient-Derived Glioblastoma with Cerebral Organoids. Cell Rep (2019) 26(12):3203–11. doi: 10.1016/j.celrep.2019.02.063
Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell (2006) 9(5):391–403. doi: 10.1016/j.ccr.2006.03.030
Brewer GJ, Torricelli JR, Evege EK, Price PJ. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. J Neurosci Res (1993) 35(5):567–76. doi: 10.1002/jnr.490350513
Baskaran S, Mayrhofer M, Kultima HG, Bergstrom T, Elfineh L, Cavelier L, et al. Primary glioblastoma cells for precision medicine: a quantitative portrait of genomic (in)stability during the first 30 passages. Neuro Oncol (2018) 20(8):1080–91. doi: 10.1093/neuonc/noy024
Jayakrishnan PC, Venkat EH, Ramachandran GM, Kesavapisharady KK, Nair SN, Bharathan B, et al. In vitro neurosphere formation correlates with poor survival in glioma. IUBMB Life (2019) 71(2):244–53. doi: 10.1002/iub.1964
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. doi: 10.1002/stem.261
Mori H, Ninomiya K, Kino-oka M, Shofuda T, Islam MO, Yamasaki M, et al. Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. J Neurosci Res (2006) 84(8):1682–91. doi: 10.1002/jnr.21082
Ladiwala U, Basu H, Mathur D. Assembling neurospheres: dynamics of neural progenitor/stem cell aggregation probed using an optical trap. PLoS One (2012) 7(6):e38613. doi: 10.1371/journal.pone.0038613
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell (2009) 4(6):568–80. doi: 10.1016/j.stem.2009.03.014
Fael Al-Mayhani TM, Ball SL, Zhao JW, Fawcett J, Ichimura K, Collins PV, et al. An efficient method for derivation and propagation of glioblastoma cell lines that conserves the molecular profile of their original tumours. J Neurosci Methods (2009) 176(2):192–9. doi: 10.1016/j.jneumeth.2008.07.022
Rahman M, Reyner K, Deleyrolle L, Millette S, Azari H, Day BW, et al. Neurosphere and adherent culture conditions are equivalent for malignant glioma stem cell lines. Anat Cell Biol (2015) 48(1):25–35. doi: 10.5115/acb.2015.48.1.25
Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, et al. Direct orthotopic transplantation of fresh surgical specimen preserves CD133+ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells (2008) 26(6):1414–24. doi: 10.1634/stemcells.2007-1009
Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, et al. Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol (2012) 9(6):338–50. doi: 10.1038/nrclinonc.2012.61
Joo KM, Kim J, Jin J, Kim M, Seol HJ, Muradov J, et al. Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ. Cell Rep (2013) 3(1):260–73. doi: 10.1016/j.celrep.2012.12.013
Patrizii M, Bartucci M, Pine SR, Sabaawy HE. Utility of Glioblastoma Patient-Derived Orthotopic Xenografts in Drug Discovery and Personalized Therapy. Front Oncol (2018) 8:23. doi: 10.3389/fonc.2018.00023
Ashizawa T, Miyata H, Iizuka A, Komiyama M, Oshita C, Kume A, et al. Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma. Int J Oncol (2013) 43(1):219–27. doi: 10.3892/ijo.2013.1916
Hutchinson L, Kirk R. High drug attrition rates–where are we going wrong? Nat Rev Clin Oncol (2011) 8(4):189–90. doi: 10.1038/nrclinonc.2011.34
Son B, Lee S, Youn H, Kim E, Kim W, Youn B. The role of tumor microenvironment in therapeutic resistance. Oncotarget (2017) 8(3):3933–45. doi: 10.18632/oncotarget.13907
Khaddour K, Johanns TM, Ansstas G. The Landscape of Novel Therapeutics and Challenges in Glioblastoma Multiforme: Contemporary State and Future Directions. Pharmaceut (Basel) (2020) 13(11):389. doi: 10.3390/ph13110389
Lynes J, Sanchez V, Dominah G, Nwankwo A, Nduom E. Current Options and Future Directions in Immune Therapy for Glioblastoma. Front Oncol (2018) 8:578. doi: 10.3389/fonc.2018.00578
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev (2007) 21(21):2683–710. doi: 10.1101/gad.1596707
Holland EC, Celestino J, Dai C, Schaefer L, Sawaya RE, Fuller GN. Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet (2000) 25(1):55–7. doi: 10.1038/75596
Uhrbom L, Dai C, Celestino JC, Rosenblum MK, Fuller GN, Holland EC. Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res (2002) 62(19):5551–8.
Wei Q, Clarke L, Scheidenhelm DK, Qian B, Tong A, Sabha N, et al. High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model. Cancer Res (2006) 66(15):7429–37. doi: 10.1158/0008-5472.CAN-06-0712
Baker M. Genome interpreter vies for place in clinical market. Nature (2012) 490(7419):157. doi: 10.1038/490157a
Miyai M, Tomita H, Soeda A, Yano H, Iwama T, Hara A. Current trends in mouse models of glioblastoma. J Neurooncol (2017) 135(3):423–32. doi: 10.1007/s11060-017-2626-2
Herranz C, Fernandez F, Martin-Ibanez R, Blasco E, Crespo E, De la Fuente C, et al. Spontaneously Arising Canine Glioma as a Potential Model for Human Glioma. J Comp Pathol (2016) 154(2-3):169–79. doi: 10.1016/j.jcpa.2015.12.001
Stoica G, Lungu G, Martini-Stoica H, Waghela S, Levine J, Smith R,3. Identification of cancer stem cells in dog glioblastoma. Vet Pathol (2009) 46(3):391–406. doi: 10.1354/vp.08-VP-0218-S-FL
Candolfi M, Curtin JF, Nichols WS, Muhammad AG, King GD, Pluhar GE, et al. Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression. J Neurooncol (2007) 85(2):133–48. doi: 10.1007/s11060-007-9400-9
Chen L, Zhang Y, Yang J, Hagan JP, Li M. Vertebrate animal models of glioma: understanding the mechanisms and developing new therapies. Biochim Biophys Acta (2013) 1836(1):158–65. doi: 10.1016/j.bbcan.2013.04.003
Fernandez F, Deviers A, Dally C, Mogicato G, Delverdier M, Cauzinille L, et al. Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases. Vet J (2016) 209:125–32. doi: 10.1016/j.tvjl.2015.10.039
Eisemann T, Costa B, Strelau J, Mittelbronn M, Angel P, Peterziel H. An advanced glioma cell invasion assay based on organotypic brain slice cultures. BMC Cancer (2018) 18(1):103. doi: 10.1186/s12885-018-4007-4
Sliwa M, Markovic D, Gabrusiewicz K, Synowitz M, Glass R, Zawadzka M, et al. The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A. Brain (2007) 130(Pt 2):476–89. doi: 10.1093/brain/awl263
Marques-Torrejon MA, Gangoso E, Pollard SM. Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture. Dis Model Mech (2018) 11(2):dmm031435. doi: 10.1242/dmm.031435
Ravi VM, Joseph K, Wurm J, Behringer S, Garrelfs N, d’Errico P, et al. Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology. Life Sci Alliance (2019) 2(4):e201900305. doi: 10.26508/lsa.201900305
Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science (2014) 345(6194):1247125. doi: 10.1126/science.1247125
Clevers H. Modeling Development and Disease with Organoids. Cell (2016) 165(7):1586–97. doi: 10.1016/j.cell.2016.05.082
Chen HI, Song H, Ming GL. Applications of Human Brain Organoids to Clinical Problems. Dev Dyn (2019) 248(1):53–64. doi: 10.1002/dvdy.24662
Sasai Y. Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell (2013) 12(5):520–30. doi: 10.1016/j.stem.2013.04.009
Huch M, Koo BK. Modeling mouse and human development using organoid cultures. Development (2015) 142(18):3113–25. doi: 10.1242/dev.118570
Hubert CG, Rivera M, Spangler LC, Wu Q, Mack SC, Prager BC, et al. Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo. Cancer Res (2016) 76(8):2465–77. doi: 10.1158/0008-5472.CAN-15-2402
da Silva B, Mathew RK, Polson ES, Williams J, Wurdak H. Spontaneous Glioblastoma Spheroid Infiltration of Early-Stage Cerebral Organoids Models Brain Tumor Invasion. SLAS Discov (2018) 23(8):862–8. doi: 10.1177/2472555218764623
Ogawa J, Pao GM, Shokhirev MN, Verma IM. Glioblastoma Model Using Human Cerebral Organoids. Cell Rep (2018) 23(4):1220–9. doi: 10.1016/j.celrep.2018.03.105
Bian S, Repic M, Guo Z, Kavirayani A, Burkard T, Bagley JA, et al. Genetically engineered cerebral organoids model brain tumor formation. Nat Methods (2018) 15(8):631–9. doi: 10.1038/s41592-018-0070-7
Krieger TG, Tirier SM, Park J, Jechow K, Eisemann T, Peterziel H, et al. Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics. Neuro Oncol (2020) 22(8):1138–49. doi: 10.1093/neuonc/noaa091
Hwang JW, Loisel-Duwattez J, Desterke C, Latsis T, Pagliaro S, Griscelli F, et al. A novel neuronal organoid model mimicking glioblastoma (GBM) features from induced pluripotent stem cells (iPSC). Biochim Biophys Acta Gen Subj (2020) 1864(4):129540. doi: 10.1016/j.bbagen.2020.129540
Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, et al. Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. Cell (2020) 180(1):188–204.e22. doi: 10.1016/j.cell.2019.11.036
Zhang C, Jin M, Zhao J, Chen J, Jin W. Organoid models of glioblastoma: advances, applications and challenges. Am J Cancer Res (2020) 10(8):2242–57.
Perrin SL, Samuel MS, Koszyca B, Brown MP, Ebert LM, Oksdath M, et al. Glioblastoma heterogeneity and the tumour microenvironment: implications for preclinical research and development of new treatments. Biochem Soc Trans (2019) 47(2):625–38. doi: 10.1042/BST20180444
Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science (2018) 359(6378):920–6. doi: 10.1126/science.aao2774
Ooft SN, Weeber F, Dijkstra KK, McLean CM, Kaing S, van Werkhoven E, et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci Trans Med (2019) 11(513):eaay2574. doi: 10.1126/scitranslmed.aay2574
Ganesh K, Wu C, O’Rourke KP, Szeglin BC, Zheng Y, Sauve CG, et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med (2019) 25(10):1607–14. doi: 10.1038/s41591-019-0584-2
da Hora CC, Schweiger MW, Wurdinger T, Tannous BA. Patient-Derived Glioma Models: From Patients to Dish to Animals. Cells (2019) 8(10):1177. doi: 10.3390/cells8101177
Roseti L, Cavallo C, Desando G, Parisi V, Petretta M, Bartolotti I, et al. Three-Dimensional Bioprinting of Cartilage by the Use of Stem Cells: A Strategy to Improve Regeneration. Mater (Basel) (2018) 10(10):679. doi: 10.3390/ma11091749
Heinrich MA, Bansal R, Lammers T, Zhang YS, Michel Schiffelers R, Prakash J. 3D-Bioprinted Mini-Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics. Adv Mater (2019) 31(14):e1806590. doi: 10.1002/adma.201806590
Ananthanarayanan B, Kim Y, Kumar S. Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform. Biomaterials (2011) 32(31):7913–23. doi: 10.1016/j.biomaterials.2011.07.005
Xiao W, Zhang R, Sohrabi A, Ehsanipour A, Sun S, Liang J, et al. Brain-Mimetic 3D Culture Platforms Allow Investigation of Cooperative Effects of Extracellular Matrix Features on Therapeutic Resistance in Glioblastoma. Cancer Res (2018) 78(5):1358–70. doi: 10.1158/0008-5472.CAN-17-2429
Hermida MA, Kumar JD, Schwarz D, Laverty KG, Di Bartolo A, Ardron M, et al. Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models. Adv Biol Regul (2020) 75:100658. doi: 10.1016/j.jbior.2019.100658
Tang M, Xie Q, Gimple RC, Zhong Z, Tam T, Tian J, et al. Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions. Cell Res (2020) 30(10):833–53. doi: 10.1038/s41422-020-0338-1
Tateishi K, Wakimoto H, Iafrate AJ, Tanaka S, Loebel F, Lelic N, et al. Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion. Cancer Cell (2015) 28(6):773–84. doi: 10.1016/j.ccell.2015.11.006
Szabo E, Schneider H, Seystahl K, Rushing EJ, Herting F, Weidner KM, et al. Autocrine VEGFR1 and VEGFR2 signaling promotes survival in human glioblastoma models in vitro and in vivo. Neuro Oncol (2016) 18(9):1242–52. doi: 10.1093/neuonc/now043
Sharpe MA, Livingston AD, Gist TL, Ghosh P, Han J, Baskin DS. Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug. EBioMedicine (2015) 2(9):1122–32. doi: 10.1016/j.ebiom.2015.08.013
Zhang C, Burger MC, Jennewein L, Genssler S, Schonfeld K, Zeiner P, et al. ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma. J Natl Cancer Institute (2016) 108(5). doi: 10.1093/jnci/djv375
Parrish KE, Cen L, Murray J, Calligaris D, Kizilbash S, Mittapalli RK, et al. Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is Limited by Ineffective Drug Penetration into the Central Nervous System. Mol Cancer Ther (2015) 14(12):2735–43. doi: 10.1158/1535-7163.MCT-15-0553
Garros-Regulez L, Aldaz P, Arrizabalaga O, Moncho-Amor V, Carrasco-Garcia E, Manterola L, et al. mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance. Expert Opin Ther Targets (2016) 20(4):393–405. doi: 10.1517/14728222.2016.1151002
Karpel-Massler G, Ishida CT, Bianchetti E, Shu C, Perez-Lorenzo R, Horst B, et al. Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses. Cancer Res (2017) 77(13):3513–26. doi: 10.1158/0008-5472.CAN-16-3424
Yuan AL, Ricks CB, Bohm AK, Lun X, Maxwell L, Safdar S, et al. ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts. PLoS One (2018) 13(8):e0202860. doi: 10.1371/journal.pone.0202860
Chang HH, Cheng YC, Tsai WC, Tsao MJ, Chen Y. Pyr3 Induces Apoptosis and Inhibits Migration in Human Glioblastoma Cells. Cell Physiol Biochem (2018) 48(4):1694–702. doi: 10.1159/000492293
Sun Y, Sun Y, Yan K, Li Z, Xu C, Geng Y, et al. Potent anti-tumor efficacy of palbociclib in treatment-naive H3.3K27M-mutant diffuse intrinsic pontine glioma. EBioMedicine (2019) 43:171–9. doi: 10.1016/j.ebiom.2019.04.043
Bejarano L, Schuhmacher AJ, Mendez M, Megias D, Blanco-Aparicio C, Martinez S, et al. Inhibition of TRF1 Telomere Protein Impairs Tumor Initiation and Progression in Glioblastoma Mouse Models and Patient-Derived Xenografts. Cancer Cell (2017) 32(5):590–607.e4. doi: 10.1016/j.ccell.2017.10.006
Guo XD, Ji J, Xue TF, Sun YQ, Guo RB, Cheng H, et al. FTY720 Exerts Anti-Glioma Effects by Regulating the Glioma Microenvironment Through Increased CXCR4 Internalization by Glioma-Associated Microglia. Front Immunol (2020) 11:178. doi: 10.3389/fimmu.2020.00178
Gravina GL, Mancini A, Colapietro A, Delle Monache S, Sferra R, Pompili S, et al. The Brain Penetrating and Dual TORC1/TORC2 Inhibitor, RES529, Elicits Anti-Glioma Activity and Enhances the Therapeutic Effects of Anti-Angiogenetic Compounds in Preclinical Murine Models. Cancers (2019) 11(10):1604. doi: 10.3390/cancers11101604
Zalles M, Smith N, Ziegler J, Saunders D, Remerowski S, Thomas L, et al. Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model. J Cell Mol Med (2020) 24(2):1738–49. doi: 10.1111/jcmm.14867
Jensen KV, Hao X, Aman A, Luchman HA, Weiss S. EGFR blockade in GBM brain tumor stem cells synergizes with JAK2/STAT3 pathway inhibition to abrogate compensatory mechanisms in vitro and in vivo. Neuro-Oncol Adv (2020) 2(1):vdaa020. doi: 10.1093/noajnl/vdaa020
Yang W, Xiu Z, He Y, Huang W, Li Y, Sun T. Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death. Cell Death Dis (2020) 11(9):786. doi: 10.1038/s41419-020-03000-z
Azzarelli R. Organoid Models of Glioblastoma to Study Brain Tumor Stem Cells. Front Cell Dev Biol (2020) 8:220. doi: 10.3389/fcell.2020.00220
Ledur PF, Onzi GR, Zong H, Lenz G. Culture conditions defining glioblastoma cells behavior: what is the impact for novel discoveries? Oncotarget (2017) 8(40):69185–97. doi: 10.18632/oncotarget.20193
Pastrana E, Cheng LC, Doetsch F. Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci U S A (2009) 106(15):6387–92. doi: 10.1073/pnas.0810407106
Torroglosa A, Murillo-Carretero M, Romero-Grimaldi C, Matarredona ER, Campos-Caro A, Estrada C. Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway. Stem Cells (2007) 25(1):88–97. doi: 10.1634/stemcells.2006-0131
Rabaneda LG, Carrasco M, Lopez-Toledano MA, Murillo-Carretero M, Ruiz FA, Estrada C, et al. Homocysteine inhibits proliferation of neuronal precursors in the mouse adult brain by impairing the basic fibroblast growth factor signaling cascade and reducing extracellular regulated kinase 1/2-dependent cyclin E expression. FASEB J (2008) 22(11):3823–35. doi: 10.1096/fj.08-109306
Bull ND, Bartlett PF. The adult mouse hippocampal progenitor is neurogenic but not a stem cell. J Neurosci (2005) 25(47):10815–21. doi: 10.1523/JNEUROSCI.3249-05.2005
Dominguez-Garcia S, Geribaldi-Doldan N, Gomez-Oliva R, Ruiz FA, Carrascal L, Bolivar J, et al. A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries. Cell Death Dis (2020) 11(4):262. doi: 10.1038/s41419-020-2453-9
Hong X, Chedid K, Kalkanis SN. Glioblastoma cell line-derived spheres in serumcontaining medium versus serum-free medium: a comparison of cancer stem cell properties. Int J Oncol (2012) 41(5):1693–700. doi: 10.3892/ijo.2012.1592
Xie Y, Bergstrom T, Jiang Y, Johansson P, Marinescu VD, Lindberg N, et al. The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes. EBioMedicine (2015) 2(10):1351–63. doi: 10.1016/j.ebiom.2015.08.026
Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol (2020) 13(1):4. doi: 10.1186/s13045-019-0829-z
Engebraaten O, Hjortland GO, Hirschberg H, Fodstad O. Growth of precultured human glioma specimens in nude rat brain. J Neurosurg (1999) 90(1):125–32. doi: 10.3171/jns.1999.90.1.0125
Mahesparan R, Read TA, Lund-Johansen M, Skaftnesmo KO, Bjerkvig R, Engebraaten O. Expression of extracellular matrix components in a highly infiltrative in vivo glioma model. Acta Neuropathol (2003) 105(1):49–57. doi: 10.1007/s00401-002-0610-0
Plowman J, Waud WR, Koutsoukos AD, Rubinstein LV, Moore TD, Grever MR. Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res (1994) 54(14):3793–9.
Kessler JD, Kahle KT, Sun T, Meerbrey KL, Schlabach MR, Schmitt EM, et al. A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis. Science (2012) 335(6066):348–53. doi: 10.1126/science.1212728
Network TC. Corrigendum: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature (2013) 494(7438):506. doi: 10.1038/nature11903
Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science (2008) 321(5897):1807–12. doi: 10.1126/science.1164382
An Z, Aksoy O, Zheng T, Fan QW, Weiss WA. Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene (2018) 37(12):1561–75. doi: 10.1038/s41388-017-0045-7
de Groot J, Milano V. Improving the prognosis for patients with glioblastoma: the rationale for targeting Src. J Neurooncol (2009) 95(2):151–63. doi: 10.1007/s11060-009-9916-2
Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature (2008) 455(7216):1061–8. doi: 10.1038/nature07385
Weissenberger J, Steinbach JP, Malin G, Spada S, Rulicke T, Aguzzi A. Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice. Oncogene (1997) 14(17):2005–13. doi: 10.1038/sj.onc.1201168
Ding H, Roncari L, Shannon P, Wu X, Lau N, Karaskova J, et al. Astrocyte-specific expression of activated p21-ras results in malignant astrocytoma formation in a transgenic mouse model of human gliomas. Cancer Res (2001) 61(9):3826–36.
Ding H, Shannon P, Lau N, Wu X, Roncari L, Baldwin RL, et al. Oligodendrogliomas result from the expression of an activated mutant epidermal growth factor receptor in a RAS transgenic mouse astrocytoma model. Cancer Res (2003) 63(5):1106–13.
Bardella C, Al-Dalahmah O, Krell D, Brazauskas P, Al-Qahtani K, Tomkova M, et al. Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis. Cancer Cell (2016) 30(4):578–94. doi: 10.1016/j.ccell.2016.08.017
Marumoto T, Tashiro A, Friedmann-Morvinski D, Scadeng M, Soda Y, Gage FH, et al. Development of a novel mouse glioma model using lentiviral vectors. Nat Med (2009) 15(1):110–6. doi: 10.1038/nm.1863
Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, et al. Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell (2009) 15(1):45–56. doi: 10.1016/j.ccr.2008.12.006
Zhu Y, Guignard F, Zhao D, Liu L, Burns DK, Mason RP, et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell (2005) 8(2):119–30. doi: 10.1016/j.ccr.2005.07.004
Xiao W, Sohrabi A, Seidlits SK. Integrating the glioblastoma microenvironment into engineered experimental models. Future Sci OA (2017) 3(3):FSO189. doi: 10.4155/fsoa-2016-0094
Caragher SP, Shireman JM, Huang M, Miska J, Atashi F, Baisiwala S, et al. Activation of Dopamine Receptor 2 Prompts Transcriptomic and Metabolic Plasticity in Glioblastoma. J Neurosci (2019) 39(11):1982–93. doi: 10.1523/JNEUROSCI.1589-18.2018
Gomez-Roman N, Stevenson K, Gilmour L, Hamilton G, Chalmers AJ. A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses. Neuro Oncol (2017) 19(2):229–41. doi: 10.1093/neuonc/now164
Weil S, Osswald M, Solecki G, Grosch J, Jung E, Lemke D, et al. Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas. Neuro Oncol (2017) 19(10):1316–26. doi: 10.1093/neuonc/nox070
Rape A, Ananthanarayanan B, Kumar S. Engineering strategies to mimic the glioblastoma microenvironment. Adv Drug Deliv Rev (2014) 79-80:172–83. doi: 10.1016/j.addr.2014.08.012
Bolivar JM, Wiesbauer J, Nidetzky B. Biotransformations in microstructured reactors: more than flowing with the stream? Trends Biotechnol (2011) 29(7):333–42. doi: 10.1016/j.tibtech.2011.03.005
Olubajo F, Achawal S, Greenman J. Development of a Microfluidic Culture Paradigm for Ex Vivo Maintenance of Human Glioblastoma Tissue: A New Glioblastoma Model? Transl Oncol (2020) 13(1):1–10. doi: 10.1016/j.tranon.2019.09.002
Li Q, Lin H, Rauch J, Deleyrolle LP, Reynolds BA, Viljoen HJ, et al. Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System. Sci Rep (2018) 8(1):3531. doi: 10.1038/s41598-018-21927-4
Ayuso JM, Monge R, Martinez-Gonzalez A, Virumbrales-Munoz M, Llamazares GA, Berganzo J, et al. Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events. Neuro Oncol (2017) 19(4):503–13. doi: 10.1093/neuonc/now230
Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc (2014) 9(10):2329–40. doi: 10.1038/nprot.2014.158
Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, et al. Cerebral organoids model human brain development and microcephaly. Nature (2013) 501(7467):373–9. doi: 10.1038/nature12517
Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, et al. Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell (2016) 165(5):1238–54. doi: 10.1016/j.cell.2016.04.032
Roesch S, Rapp C, Dettling S, Herold-Mende C. When Immune Cells Turn Bad-Tumor-Associated Microglia/Macrophages in Glioma. Int J Mol Sci (2018) 19(2):436. doi: 10.3390/ijms19020436
Malesci A, Bianchi P, Celesti G, Basso G, Marchesi F, Grizzi F, et al. Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. Oncoimmunology (2017) 6(12):e1342918. doi: 10.1080/2162402X.2017.1342918
Allavena P, Sica A, Garlanda C, Mantovani A. The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev (2008) 222:155–61. doi: 10.1111/j.1600-065X.2008.00607.x
