Advertisement

Development of a Patient-Derived Xenograft Model Using Brain Tumor Stem Cell Systems to Study Cancer

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1458)

Abstract

Patient-derived xenograft (PDX) models provide an excellent platform to understand cancer initiation and development in vivo. In the context of brain tumor initiating cells (BTICs), PDX models allow for characterization of tumor formation, growth, and recurrence, in a clinically relevant in vivo system. Here, we detail procedures to harvest, culture, characterize, and orthotopically inject human BTICs derived from patient samples.

Key words

Patient-derived xenograft (PDX) Brain tumor-initiating cell (BTIC) Flow cytometry In vitro self-renewal assay In vitro proliferation assay Lentivirus Intracranial injections Immunohistochemistry NOD-SCID 

References

  1. 1.
    Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111CrossRefPubMedGoogle Scholar
  2. 2.
    Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902CrossRefPubMedGoogle Scholar
  3. 3.
    Swanton C (2012) Intratumor heterogeneity: evolution through space and time. Cancer Res 72:4875–4882CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cox CV, Diamanti P, Evely RS, Kearns PR, Blair A (2009) Expression of CD133 on leukemia-initiating cells in childhood ALL. Blood 113:3287–3296CrossRefPubMedGoogle Scholar
  5. 5.
    Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M et al (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1:313–323CrossRefPubMedGoogle Scholar
  6. 6.
    O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110CrossRefPubMedGoogle Scholar
  7. 7.
    Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401CrossRefPubMedGoogle Scholar
  8. 8.
    Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951CrossRefPubMedGoogle Scholar
  9. 9.
    Xin L, Lawson DA, Witte ON (2005) The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci U S A 102:6942–6947CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Batts TD, Machado HL, Zhang Y, Creighton CJ, Li Y, Rosen JM (2011) Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration. PLoS One 6:e27841CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Seigel GM, Campbell LM, Narayan M, Gonzalez-Fernandez F (2005) Cancer stem cell characteristics in retinoblastoma. Mol Vis 11:729–737PubMedGoogle Scholar
  12. 12.
    Du L, Wang H, He L, Zhang J, Ni B, Wang X et al (2008) CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 14:6751–6760CrossRefPubMedGoogle Scholar
  13. 13.
    Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25:1696–1708CrossRefPubMedGoogle Scholar
  14. 14.
    Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V et al (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037CrossRefPubMedGoogle Scholar
  15. 15.
    Baumann P, Cremers N, Kroese F, Orend G, Chiquet-Ehrismann R, Uede T et al (2005) CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res 65:10783–10793CrossRefPubMedGoogle Scholar
  16. 16.
    Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW et al (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 104:10158–10163CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100:15178–15183CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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 63:5821–5828PubMedGoogle Scholar
  19. 19.
    Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021CrossRefPubMedGoogle Scholar
  20. 20.
    Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760CrossRefPubMedGoogle Scholar
  21. 21.
    Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR et al (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B et al (2007) A perivascular niche for brain tumor stem cells. Cancer Cell 11:69–82CrossRefPubMedGoogle Scholar
  23. 23.
    Kaye AH, Morstyn G, Gardner I, Pyke K (1986) Development of a xenograft glioma model in mouse brain. Cancer Res 46:1367–1373PubMedGoogle Scholar
  24. 24.
    Rana MW, Pinkerton H, Thornton H, Nagy D (1977) Heterotransplantation of human glioblastoma multiforme and meningioma to nude mice. Proc Soc Exp Biol Med 155:85–88CrossRefPubMedGoogle Scholar
  25. 25.
    Shapiro WR, Basler GA, Chernik NL, Posner JB (1979) Human brain tumor transplantation into nude mice. J Natl Cancer Inst 62:447–453PubMedGoogle Scholar
  26. 26.
    Shultz LD, Brehm MA, Bavari S, Greiner DL (2011) Humanized mice as a preclinical tool for infectious disease and biomedical research. Ann N Y Acad Sci 1245:50–54CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.McMaster Stem Cell and Cancer Research InstituteMcMaster UniversityHamiltonCanada
  2. 2.Department of Biochemistry and Biomedical Sciences, Faculty of Health SciencesMcMaster UniversityHamiltonCanada
  3. 3.Department of Surgery, Faculty of Health SciencesMcMaster UniversityHamiltonCanada

Personalised recommendations