Top

Published in:

01-08-2016 | Laboratory Investigation

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation

Authors: Magdalena Ciezka, Milena Acosta, Cristina Herranz, Josep M. Canals, Martí Pumarola, Ana Paula Candiota, Carles Arús

Published in: Journal of Neuro-Oncology | Issue 1/2016

Abstract

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/−) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

Available only for authorised users

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109. doi:10.1007/s00401-007-0243-4 CrossRefPubMedPubMedCentral

Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, Stroup NE, Kruchko C, Barnholtz-Sloan JS (2013) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2006–2010. Neuro-oncol 15(Suppl 2):ii1–ii56. doi:10.1093/neuonc/not151 PubMedPubMedCentral

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMed

Nieder C, Grosu AL, Mehta MP, Andratschke N, Molls M (2004) Treatment of malignant gliomas: radiotherapy, chemotherapy and integration of new targeted agents. Expert Rev Neurother 4(4):691–703. doi:10.1586/14737175.4.4.691 CrossRefPubMed

Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr (2004) Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Int J Radiat Oncol Biol Phys 58(4):1147–1152. doi:10.1016/j.ijrobp.2003.08.024 CrossRefPubMed

van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T (2006) Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol 24(18):2715–2722. doi:10.1200/JCO.2005.04.6078 CrossRefPubMed

Weiss WA, Burns MJ, Hackett C, Aldape K, Hill JR, Kuriyama H, Kuriyama N, Milshteyn N, Roberts T, Wendland MF, DePinho R, Israel MA (2003) Genetic determinants of malignancy in a mouse model for oligodendroglioma. Cancer Res 63(7):1589–1595PubMed

Hu X, Pandolfi PP, Li Y, Koutcher JA, Rosenblum M, Holland EC (2005) mTOR promotes survival and astrocytic characteristics induced by Pten/AKT signaling in glioblastoma. Neoplasia 7(4):356–368CrossRefPubMedPubMedCentral

Alcoser SY, Hollingshead MG (2011) Genetically engineered mouse models in Preclinical Anti-Cancer Drug Development. In: Kapetanović I (ed) Drug discovery and development-present and future. InTech. http://www.intechopen.com/books/drug-discovery-and-development-present-and-future/genetically-engineered-mouse-models-in-preclinical-anti-cancer-drug-development. Accessed on 28 Dec 2015

10.

Cha S, Johnson G, Wadghiri YZ, Jin O, Babb J, Zagzag D, Turnbull DH (2003) Dynamic, contrast-enhanced perfusion MRI in mouse gliomas: correlation with histopathology. Magn Reson Med 49(5):848–855. doi:10.1002/mrm.10446 CrossRefPubMed

11.

Szatmari T, Lumniczky K, Desaknai S, Trajcevski S, Hidvegi EJ, Hamada H, Safrany G (2006) Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci 97(6):546–553. doi:10.1111/j.1349-7006.2006.00208.x CrossRefPubMed

12.

Smilowitz HM, Weissenberger J, Weis J, Brown JD, O’Neill RJ, Laissue JA (2007) Orthotopic transplantation of v-src-expressing glioma cell lines into immunocompetent mice: establishment of a new transplantable in vivo model for malignant glioma. J Neurosurg 106(4):652–659. doi:10.3171/jns.2007.106.4.652 CrossRefPubMed

13.

El Meskini R, Iacovelli AJ, Kulaga A, Gumprecht M, Martin PL, Baran M, Householder DB, Van Dyke T, Weaver Ohler Z (2015) A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors. Dis Model Mech 8(1):45–56. doi:10.1242/dmm.018168 CrossRefPubMed

14.

Borges AR, Lopez-Larrubia P, Marques JB, Cerdan SG (2012) MR imaging features of high-grade gliomas in murine models: how they compare with human disease, reflect tumor biology, and play a role in preclinical trials. Am J Neuroradiol 33(1):24–36. doi:10.3174/ajnr.A2959 CrossRefPubMed

15.

Brandes AA, Tosoni A, Franceschi E, Reni M, Gatta G, Vecht C (2008) Glioblastoma in adults. Crit Rev Oncol Hematol 67 (2):139–152. doi:10.1016/j.critrevonc.2008.02.005 CrossRefPubMed

16.

Majos C, Alonso J, Aguilera C, Serrallonga M, Perez-Martin J, Acebes JJ, Arus C, Gili J (2003) Proton magnetic resonance spectroscopy ((1)H MRS) of human brain tumours: assessment of differences between tumour types and its applicability in brain tumour categorization. Eur Radiol 13(3):582–591. doi:10.1007/s00330-002-1547-3 PubMed

17.

Sibtain NA, Howe FA, Saunders DE (2007) The clinical value of proton magnetic resonance spectroscopy in adult brain tumours. Clin Radiol 62(2):109–119. doi:10.1016/j.crad.2006.09.012 CrossRefPubMed

18.

Martinez-Bisbal MC, Celda B (2009) Proton magnetic resonance spectroscopy imaging in the study of human brain cancer. Q J Nucl Med Mol Imaging 53(6):618–630PubMed

19.

Nelson SJ, Graves E, Pirzkall A, Li X, Antiniw Chan A, Vigneron DB, McKnight TR (2002) In vivo molecular imaging for planning radiation therapy of gliomas: an application of 1 H MRSI. J Magn Reson Imaging 16(4):464–476. doi:10.1002/jmri.10183 CrossRefPubMed

20.

Nelson SJ, Vigneron DB, Dillon WP (1999) Serial evaluation of patients with brain tumors using volume MRI and 3D 1 H MRSI. NMR Biomed 12(3):123–138. doi:10.1002/(SICI)1099-1492(199905)12:3<123::AID-NBM541>3.0.CO;2-Y CrossRefPubMed

21.

Delgado-Goni T, Martin-Sitjar J, Simoes RV, Acosta M, Lope-Piedrafita S, Arus C (2013) Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors. NMR Biomed 26(2):173–184. doi:10.1002/nbm.2832 CrossRefPubMed

22.

Simoes RV, Garcia-Martin ML, Cerdan S, Arus C (2008) Perturbation of mouse glioma MRS pattern by induced acute hyperglycemia. NMR Biomed 21(3):251–264. doi:10.1002/nbm.1188 CrossRefPubMed

23.

Simoes RV, Delgado-Goni T, Lope-Piedrafita S, Arus C (2010) 1 H-MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia. NMR Biomed 23(1):23–33. doi:10.1002/nbm.1421 CrossRefPubMed

24.

https://mouse.ncifcrf.gov/available_details.asp?ID=01XD3. Accessed on 28 Dec 2015

25.

Acosta M (2013) Mejora de los modelos preclínicos de tumores cerebrales. Aplicación a la caracterización ex vivo e in vivo de agentes de contraste nanoparticulados para imagen de resonancia magnetica. Universitat Autònoma de Barcelona. http://hdl.handle.net/10803/128995. Accessed on 28 Dec 2015

26.

Ciezka M (2015) Improvement of protocols for brain cancer diagnosis and therapy response monitoring using magnetic resonance based molecular imaging strategies. Universitat Autònoma de Barcelona

27.

Delgado-Goni T, Julia-Sape M, Candiota AP, Pumarola M, Arus C (2014) Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma. NMR Biomed 27(11):1333–1345. doi:10.1002/nbm.3194 CrossRefPubMed

28.

Simoes RV, Ortega-Martorell S, Delgado-Goni T, Le Fur Y, Pumarola M, Candiota AP, Martin J, Stoyanova R, Cozzone PJ, Julia-Sape M, Arus C (2012) Improving the classification of brain tumors in mice with perturbation enhanced (PE)-MRSI. Integr Biol 4 (2):183–191. doi:10.1039/c2ib00079b CrossRef

29.

Masters JRW, Palsson B (2002) Human cell culture. Cancer cell lines. Kluwer, New YorkCrossRef

30.

Yi L, Zhou C, Wang B, Chen T, Xu M, Xu L, Feng H (2013) Implantation of GL261 neurospheres into C57/BL6 mice: a more reliable syngeneic graft model for research on glioma-initiating cells. Int J Oncol 43(2):477–484. doi:10.3892/ijo.2013.1962 PubMed

31.

Mullins CS, Schneider B, Stockhammer F, Krohn M, Classen CF, Linnebacher M (2013) Establishment and characterization of primary glioblastoma cell lines from fresh and frozen material: a detailed comparison. PloS one 8(8):e71070. doi:10.1371/journal.pone.0071070 CrossRefPubMedPubMedCentral

32.

Shimada Y, Maeda M, Watanabe G, Yamasaki S, Komoto I, Kaganoi J, Kan T, Hashimoto Y, Imoto I, Inazawa J, Imamura M (2003) Cell culture in esophageal squamous cell carcinoma and the association with molecular markers. Clin Cancer Res 9(1):243–249PubMed

33.

Barker M, Hoshino T, Gurcay O, Wilson CB, Nielsen SL, Downie R, Eliason J (1973) Development of an animal brain tumor model and its response to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea. Cancer Res 33(5):976–986PubMed

34.

Halfter H, Kremerskothen J, Weber J, Hacker-Klom U, Barnekow A, Ringelstein EB, Stogbauer F (1998) Growth inhibition of newly established human glioma cell lines by leukemia inhibitory factor. J Neurooncol 39(1):1–18. doi:10.1023/A:1005901423332 CrossRefPubMed

35.

Onda K, Nagai S, Tanaka R, Morii K, Yoshimura JI, Tsumanuma I, Kumanishi T (1999) Establishment of two glioma cell lines from two surgical specimens obtained at different times from the same individual. J Neurooncol 41(3):247–254. doi:10.1023/A:1006172608019 CrossRefPubMed

36.

Goike HM, Asplund AC, Pettersson EH, Liu L, Ichimura K, Collins VP (2000) Cryopreservation of viable human glioblastoma xenografts. Neuropathol Appl Neurobiol 26(2):172–176. doi:10.1046/j.1365-2990.2000.026002172.x CrossRefPubMed

37.

Sundlisaeter E, Wang J, Sakariassen PO, Marie M, Mathisen JR, Karlsen BO, Prestegarden L, Skaftnesmo KO, Bjerkvig R, Enger PO (2006) Primary glioma spheroids maintain tumourogenicity and essential phenotypic traits after cryopreservation. Neuropathol Appl Neurobiol 32(4):419–427. doi:10.1111/j.1365-2990.2006.00744.x CrossRefPubMed

38.

Chong YK, Toh TB, Zaiden N, Poonepalli A, Leong SH, Ong CE, Yu Y, Tan PB, See SJ, Ng WH, Ng I, Hande MP, Kon OL, Ang BT, Tang C (2009) Cryopreservation of neurospheres derived from human glioblastoma multiforme. Stem cells 27(1):29–39. doi:10.1634/stemcells.2008-0009 CrossRefPubMedPubMedCentral

39.

Heiss WD, Raab P, Lanfermann H (2011) Multimodality assessment of brain tumors and tumor recurrence. J Nucl Med 52(10):1585–1600. doi:10.2967/jnumed.110.084210 CrossRefPubMed

Title: Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation
Authors: Magdalena Ciezka
Milena Acosta
Cristina Herranz
Josep M. Canals
Martí Pumarola
Ana Paula Candiota
Carles Arús
Publication date: 01-08-2016
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2164-3

At a glance: The STEP trials

Springer Medicine

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2016

Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma

Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma

Quercetin blocks t-AUCB-induced autophagy by Hsp27 and Atg7 inhibition in glioblastoma cells in vitro

Prevalence and profile of cognitive impairment in adult glioma: a sensitivity analysis

Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma

Levetiracetam for seizure prevention in brain tumor patients: a systematic review