title: Inhibition of tumor formation and redirected differentiation of glioblastoma cells in a xenotypic embryonic environment.
abstract: BACKGROUND
  Tissue microenvironment plays key roles in regulating the progression of aggressive tumors. Tumors are uncommon in the early embryo, suggesting that embryonic tissue microenvironments are nonpermissive for tumors. Yet, the effects of embryonic tissue microenvironments on tumor cells have not been extensively studied. We have, therefore, tested the behavior of human glioblastoma multiforme (GBM) cells transplanted into a central neural tissue microenvironment in the chicken embryo.
  
  
  RESULTS
  GBM cells were cultured as spheres to enrich for GBM stem cells (GSCs) and transduced with GFP for identification. Within the proliferative embryonic neural tissue, GSC-enriched GBM cells exhibited reduced proliferation and survival, altered gene expression, and formed no tumors, in marked contrast to their aggressive behavior in vitro and tumor formation in other tissue microenvironments including the chorioallantoic membrane of the chicken embryo and the brain of adult severe combined immunodeficiency (SCID) mice. Surviving cells in the spinal neural tube exhibited tumor-atypical expression profiles of neuron-, glia-, stem cell-, and tumor-related genes.
  
  
  CONCLUSIONS
  Embryonic neural tissue provides a poor environment for GBM cell survival and tumor formation, and redirects differentiation toward a more benign phenotype. Understanding the anti-tumorigenic effects of this embryonic tissue microenvironment could provide opportunities to develop novel therapies for GBM treatment.
authors.affiliation: Laboratory of Neural Development and Optical Recording (NDEVOR), Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Joel
authors.forename: Cecilie J
authors.initials: CJ
authors.lastname: Sandberg
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
authors.forename: Einar O
authors.initials: EO
authors.lastname: Vik-Mo
authors.forename: Iver A
authors.initials: IA
authors.lastname: Langmoen
authors.forename: Joel C
authors.initials: JC
authors.lastname: Glover
mesh_terms: D000818:Animals; D002460:Cell Line; D060833:Cellular Microenvironment / Q000502:physiology*; D002642:Chick Embryo; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009417:Nerve Tissue / Q000166:cytology / Q000196:embryology*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology*
keywords: PTEN; chicken embryo; glioblastoma; glioma; tumor reprogramming