Establishing Brain Tumor Stem Cell Culture from Patient Brain Tumors and Imaging Analysis of Patient-Derived Xenografts.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9214969 Publication Model: Print Cited Medium: Internet ISSN: 1940-6029 (Electronic) Linking ISSN: 10643745 NLM ISO Abbreviation: Methods Mol Biol Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Clifton, N.J. : Humana Press,
    • Subject Terms:
      Brain Neoplasms*/pathology ; Glioblastoma*/pathology; Humans ; Mice ; Animals ; Heterografts ; Brain/metabolism ; Neoplastic Stem Cells/metabolism
    • Abstract:
      Brain tumor stem cells (BTSCs) have been isolated from different types of brain tumors including glioblastoma. Although BTSCs share common characteristics with neural stem cells (NSCs), such as capacity to self-renew and undergo long-term proliferation, they have tumor-propagating capabilities. A small population of BTSC can give rise to secondary tumor when transplanted into severe immunodeficient (SCID) mice. The histological and cytological features, as well as genetic heterogeneity of the xenografted tumors in mice, closely resemble those of primary tumors in patients. Patient-derived xenografts (PDX), therefore, provide a clinically relevant model to study brain tumors. Here, we describe our protocol for establishing BTSC cultures following surgical excision of human brain tumors and the procedures to conduct PDX studies in SCID mice. We also provide our detailed step-by-step protocol on in vivo imaging system (IVIS) of the PDX tumors as a noninvasive method to trace the cells and tumor volume.
      (© 2023. Springer Science+Business Media, LLC.)
    • References:
      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 352:987–996. (PMID: 10.1056/NEJMoa04333015758009)
      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 114:97–109. (PMID: 10.1007/s00401-007-0243-4176184411929165)
      Louis DN (2006) Molecular pathology of malignant gliomas. Annu Rev Pathol 1:97–117. (PMID: 10.1146/annurev.pathol.1.110304.10004318039109)
      Bernstein JJ, Woodard CA (1995) Glioblastoma cells do not intravasate into blood vessels. Neurosurgery 36:124–132. discussion 132. (PMID: 10.1227/00006123-199501000-000167708148)
      Holland EC (2001) Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet 2:120–129. (PMID: 10.1038/3505253511253051)
      Bachoo RM, Maher EA, Ligon KL, Sharpless NE, Chan SS, You MJ, Tang Y, DeFrances J, Stover E, Weissleder R, Rowitch DH, Louis DN, DePinho RA (2002) Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1:269–277. (PMID: 10.1016/S1535-6108(02)00046-612086863)
      Uhrbom L, Dai C, Celestino JC, Rosenblum MK, Fuller GN, Holland EC (2002) Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res 62:5551–5558. (PMID: 12359767)
      Bajenaru ML, Hernandez MR, Perry A, Zhu Y, Parada LF, Garbow JR, Gutmann DH (2003) Optic nerve glioma in mice requires astrocyte Nf1 gene inactivation and Nf1 brain heterozygosity. Cancer Res 63:8573–8577. (PMID: 14695164)
      Singh S, Dirks PB (2007) Brain tumor stem cells: identification and concepts. Neurosurg Clin N Am 18:31–38, viii.
      Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828. (PMID: 14522905)
      Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401. (PMID: 10.1038/nature0312815549107)
      Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021. (PMID: 10.1158/0008-5472.CAN-04-136415466194)
      Yuan X, Curtin J, Xiong Y, Liu G, Waschsmann-Hogiu S, Farkas DL, Black KL, Yu JS (2004) Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23:9392–9400. (PMID: 10.1038/sj.onc.120831115558011)
      Park DM, Rich JN (2009) Biology of glioma cancer stem cells. Mol Cells 28:7–12. (PMID: 10.1007/s10059-009-0111-219655094)
      Lathia JD, Mack SC, Mulkearns-Hubert EE, Valentim CL, Rich JN (2015) Cancer stem cells in glioblastoma. Genes Dev 29:1203–1217. (PMID: 10.1101/gad.261982.115261090464495393)
      Chen J, McKay RM, Parada LF (2012) Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell 149:36–47. (PMID: 10.1016/j.cell.2012.03.009224643223719882)
      Kaneko Y, Sakakibara S, Imai T, Suzuki A, Nakamura Y, Sawamoto K, Ogawa Y, Toyama Y, Miyata T, Okano H (2000) Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci 22:139–153. (PMID: 10.1159/00001743510657706)
      Manoranjan B, Wang X, Hallett RM, Venugopal C, Mack SC, McFarlane N, Nolte SM, Scheinemann K, Gunnarsson T, Hassell JA, Taylor MD, Lee C, Triscott J, Foster CM, Dunham C, Hawkins C, Dunn SE, Singh SK (2013) FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells. Stem Cells 31:1266–1277. (PMID: 10.1002/stem.140123592496)
      Graham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39:749–765. (PMID: 10.1016/S0896-6273(03)00497-512948443)
      Suva ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE (2014) Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell 157:580–594. (PMID: 10.1016/j.cell.2014.02.030247264344004670)
      Fasano CA, Dimos JT, Ivanova NB, Lowry N, Lemischka IR, Temple S (2007) shRNA knockdown of Bmi-1 reveals a critical role for p21-Rb pathway in NSC self-renewal during development. Cell Stem Cell 1:87–99. (PMID: 10.1016/j.stem.2007.04.00118371338)
      Abdouh M, Facchino S, Chatoo W, Balasingam V, Ferreira J, Bernier G (2009) BMI1 sustains human glioblastoma multiforme stem cell renewal. J Neurosci 29:8884–8896. (PMID: 10.1523/JNEUROSCI.0968-09.2009196056266665439)
      Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–526. (PMID: 10.1038/nature11287228547813427400)
      Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760. (PMID: 10.1038/nature0523617051156)
      Venugopal C, Hallett R, Vora P, Manoranjan B, Mahendram S, Qazi MA, McFarlane N, Subapanditha M, Nolte SM, Singh M, Bakhshinyan D, Garg N, Vijayakumar T, Lach B, Provias JP, Reddy K, Murty NK, Doble BW, Bhatia M, Hassell JA, Singh SK (2015) Pyrvinium targets CD133 in human glioblastoma brain tumor-initiating cells. Clin Cancer Res 21:5324–5337. (PMID: 10.1158/1078-0432.CCR-14-314726152745)
      Parada LF, Dirks PB, Wechsler-Reya RJ (2017) Brain tumor stem cells remain in play. J Clin Oncol 35:2428–2431. (PMID: 10.1200/JCO.2017.73.9540286407105516484)
      Singh SK, Clarke ID, Hide T, Dirks PB (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273. (PMID: 10.1038/sj.onc.120794615378086)
      Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6:425–436. (PMID: 10.1038/nrc188916723989)
      Berger F, Paulmurugan R, Bhaumik S, Gambhir SS (2008) Uptake kinetics and biodistribution of 14C-D-luciferin--a radiolabeled substrate for the firefly luciferase catalyzed bioluminescence reaction: impact on bioluminescence based reporter gene imaging. Eur J Nucl Med Mol Imaging 35:2275–2285. (PMID: 10.1007/s00259-008-0870-6186611304157642)
      Gheysens O, Gambhir SS (2005) Studying molecular and cellular processes in the intact organism. Prog Drug Res 62:117–150. (PMID: 10.1007/3-7643-7426-8_416329256)
      Bhaumik S, Gambhir SS (2002) Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci U S A 99:377–382. (PMID: 10.1073/pnas.01261109911752410)
      Contag PR, Olomu IN, Stevenson DK, Contag CH (1998) Bioluminescent indicators in living mammals. Nat Med 4:245–247. (PMID: 10.1038/nm0298-2459461201)
      Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452:580–589. (PMID: 10.1038/nature06917183857322708079)
    • Grant Information:
      183710 Canada CIHR; 179865 Canada CIHR; 162198 Canada CIHR
    • Contributed Indexing:
      Keywords: Bioluminescence; Brain tumors stem cells; Glioblastoma; In vivo imaging system; Magnetic resonance imaging; Optical imaging; Patient-derived xenografts; Reporter gene
    • Publication Date:
      Date Created: 20230527 Date Completed: 20231108 Latest Revision: 20231117
    • Publication Date:
      20240829
    • Accession Number:
      10.1007/7651_2023_482
    • Accession Number:
      37243860