Abstract
Glioblastoma multiforme is the most common, aggressive and lethal type of brain tumor, characterized by an aggressive, heterogenic and highly angiogenic behavior. Establishing mice models that mimic the etiology, biology and histopathology of human glioblastomas is of extreme importance, as they are a crucial tool to understand the tumor initiation, formation, angiogenesis, progression and metastasis. Orthotopic xenograft mice models remain in the frontline of neuro-oncology as an experimental system to identify novel therapeutic targets and to determine the efficacy of different therapeutic agents and/or nanosystems. The present chapter describes a protocol for establishing brain tumor xenografts in mice following a single injection of glioblastoma cells.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (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
Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64(6):479–489. https://doi.org/10.1093/jnen/64.6.479
Zlatescu MC, TehraniYazdi A, Sasaki H, Megyesi JF, Betensky RA, Louis DN, Cairncross JG (2001) Tumor location and growth pattern correlate with genetic signature in oligodendroglial neoplasms. Cancer Res 61(18):6713–6715
Ohgaki H, Kleihues P (2013) The definition of primary and secondary glioblastoma. Clin Cancer Res 19(4):764–772. https://doi.org/10.1158/1078-0432.CCR-12-3002
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773. https://doi.org/10.1056/NEJMoa0808710
Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009) IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15(19):6002–6007. https://doi.org/10.1158/1078-0432.CCR-09-0715
Davis ME (2016) Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs 20(5):S2–S8. https://doi.org/10.1188/16.CJON.S1.2-8
Miyai M, Tomita H, Soeda A, Yano H, Iwama T, Hara A (2017) Current trends in mouse models of glioblastoma. J Neurooncol 135(3):423–432. https://doi.org/10.1007/s11060-017-2626-2
Basso J, Miranda A, Sousa J, Pais A, Vitorino C (2018) Repurposing drugs for glioblastoma: from bench to bedside. Cancer Lett 428:173–183. https://doi.org/10.1016/j.canlet.2018.04.039
Ashburn TT, Thor KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 3(8):673–683
Zhou J, Atsina K-B, Himes BT, Strohbehn GW, Saltzman WM (2012) Novel delivery strategies for glioblastoma. Cancer J 18(1):89–99. https://doi.org/10.1097/PPO.0b013e318244d8ae
Zottel A, Videtič Paska A, Jovčevska I (2019) Nanotechnology meets oncology: nanomaterials in brain cancer research, diagnosis and therapy. Materials 12(10):1588. https://doi.org/10.3390/ma12101588
Basso J, Miranda A, Nunes S, Cova T, Sousa J, Vitorino C, Pais A (2018) Hydrogel-based drug delivery nanosystems for the treatment of brain tumors. Gels 4(3):62. https://doi.org/10.3390/gels4030062
Sulaiman A, Wang L (2017) Bridging the divide: preclinical research discrepancies between triple-negative breast cancer cell lines and patient tumors. Oncotarget 8(68):113269–113281. https://doi.org/10.18632/oncotarget.22916
Namekawa T, Ikeda K, Horie-Inoue K, Inoue S (2019) Application of prostate cancer models for preclinical study: advantages and limitations of cell lines, patient-derived xenografts, and three-dimensional culture of patient-derived cells. Cells 8(1):74. https://doi.org/10.3390/cells8010074
Williams J (2018) Using PDX for preclinical cancer drug discovery: the evolving field. J Clin Med 7(3):41. https://doi.org/10.3390/jcm7030041
Li G (2015) Patient-derived xenograft models for oncology drug discovery. J Cancer Metast Treat 1(1):8–15. https://doi.org/10.4103/2394-4722.152769
Khan FR, Henderson JM (2013) Deep brain stimulation surgical techniques. In: Handbook of clinical neurology, vol 116. Elsevier, Amsterdam, pp 27–37. https://doi.org/10.1016/B978-0-444-53497-2.00003-6
Wu M, Shu J (2018) Multimodal molecular imaging: current status and future directions. Contrast Media Mol Imaging 2018
Janib SM, Moses AS, MacKay JA (2010) Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev 62(11):1052–1063
Xia J, Wang LV (2013) Small-animal whole-body photoacoustic tomography: a review. IEEE Trans Biomed Eng 61(5):1380–1389
Moses WW (2011) Fundamental limits of spatial resolution in PET. Nucl Instrum Methods Phys Res A 648(supplement 1):S236–s240. https://doi.org/10.1016/j.nima.2010.11.092
Jost SC, Collins L, Travers S, Piwnica-Worms D, Garbow JR (2009) Measuring brain tumor growth: combined bioluminescence imaging-magnetic resonance imaging strategy. Mol Imaging 8(5):245–253
Lenting K, Verhaak R, Ter Laan M, Wesseling P, Leenders W (2017) Glioma: experimental models and reality. Acta Neuropathol 133(2):263–282
Commission E (2010) Directive 2010/63/EU of the European Parliament and of the council of 22 September 2010 on the protection of animals used for scientific purposes. Off J Eur Union 276:33–79
Costa A, Antunes L (2011) Handbook of laboratory animals: mice, rats and rabbits, vol 419. Série didáctica Ciências Aplicadas. Universidade de Trás-os-Montes e Alto Douro, Vila Real, Portugal
Paxinos G, Franklin KB (2001) Paxinos and Franklin’s the mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, Cambridge, Massachusetts
Frenster JD, Placantonakis DG (2018) Bioluminescent in vivo imaging of Orthotopic glioblastoma xenografts in mice. In: Placantonakis DG (ed) Glioblastoma: methods and protocols. Springer New York, New York, NY, pp 191–198. https://doi.org/10.1007/978-1-4939-7659-1_15
Acknowledgments
João Basso acknowledges the PhD research grant SFRH/BD/149138/2019 assigned by Fundação para a Ciência e a Tecnologia (FCT), the Portuguese Agency for Scientific Research. The authors also acknowledge FCT for the financial support through the Research Projects no. 016648 (Ref. POCI-01-0145-FEDER- 016648), Pest UID/NEU/04539/2013, COMPETE (Ref. POCI-01-0145-FEDER-007440), and CENTRO-01-0145-FEDER-030752 and the Coimbra Chemistry Centre, supported by FCT, through the Project UID/QUI/00313/2020.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Basso, J., Sereno, J., Fortuna, A., Castelo-Branco, M., Vitorino, C. (2021). Establishing Orthotopic Xenograft Glioblastoma Models for Use in Preclinical Development. In: Agrahari, V., Kim, A., Agrahari, V. (eds) Nanotherapy for Brain Tumor Drug Delivery. Neuromethods, vol 163. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1052-7_12
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1052-7_12
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-1051-0
Online ISBN: 978-1-0716-1052-7
eBook Packages: Springer Protocols