Clinical & Experimental Metastasis

, Volume 29, Issue 4, pp 371–380

Distinct patterns of human medulloblastoma dissemination in the developing chick embryo nervous system

  • Tene A. Cage
  • Jonathan D. Louie
  • Sharon R. Liu
  • Arturo Alvarez-Buylla
  • Nalin Gupta
  • Jeanette Hyer
Technical Note

DOI: 10.1007/s10585-012-9456-6

Cite this article as:
Cage, T.A., Louie, J.D., Liu, S.R. et al. Clin Exp Metastasis (2012) 29: 371. doi:10.1007/s10585-012-9456-6
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Abstract

Medulloblastoma (MB) is the most common malignant primary brain tumor in children. Aggressive tumors that disseminate along the leptomeninges carry extremely poor prognoses. Mechanisms that predict dissemination are poorly understood. Our objective was to develop a reliable and reproducible model to study MB dissemination. We have created a chicken-human xenograft to study features of MB with leptomeningeal dissemination. Human MB cell lines (D283, Daoy), primary human MB cells (SF8113), and primary genetic mouse model (Math1cre:SmoM2 flox/flox) MB cells were either transfected to express green fluorescent protein (GFP) or were labeled with a membrane permeable green fluorescent probe. Cells were then injected as aggregates or implanted as pellets into the developing chicken brain immediately after neural tube closure at embryonic day 2 (E2). Most embryos were harvested three days after implantation (E5) though some were harvested up to E15. The developing brain was analyzed via whole mount fluorescent imaging and tissue section immunohistochemistry. Human and mouse MBs survived in the developing chicken central nervous system (CNS). They exhibited distinct patterns of incorporation and dissemination into the CNS that were consistent with observed phenotypes of the corresponding human patient or mouse host. Specifically, metastatic D283 cells disseminated along the leptomeninges whereas Daoy, primary mouse MB, and primary human MB cells did not. This work supports an avian-human xenograft as a successful model to study patterns of MB dissemination. Our model provides a basis for manipulating cell signaling mechanisms to understand critical targets involved in MB dissemination.

Keywords

Brain TumorChicken embryoDisseminationMedulloblastomaPediatricXenograft

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Tene A. Cage
    • 1
  • Jonathan D. Louie
    • 2
  • Sharon R. Liu
    • 1
  • Arturo Alvarez-Buylla
    • 1
    • 3
  • Nalin Gupta
    • 1
    • 4
  • Jeanette Hyer
    • 1
  1. 1.Department of Neurological SurgeryUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Faculty of ScienceUniversity of CaliforniaBerkeleyUSA
  3. 3.Department of Neurological Surgery, Broad Center of Regeneration Medicine and Stem Cell ResearchUniversity of California, San FranciscoSan FranciscoUSA
  4. 4.Department of Neurological Surgery, Brain Tumor Research CenterUniversity of California, San FranciscoSan FranciscoUSA