Inhibition of tumor formation and redirected differentiation of glioblastoma cells in a xenotypic embryonic environment
Article first published online: 29 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 242, Issue 9, pages 1078–1093, September 2013
How to Cite
Joel, M., Sandberg, C. J., Boulland, J.-L., Vik-Mo, E. O., Langmoen, I. A. and Glover, J. C. (2013), Inhibition of tumor formation and redirected differentiation of glioblastoma cells in a xenotypic embryonic environment. Dev. Dyn., 242: 1078–1093. doi: 10.1002/dvdy.24001
- Issue published online: 20 AUG 2013
- Article first published online: 29 JUL 2013
- Accepted manuscript online: 18 JUN 2013 06:38AM EST
- Manuscript Revised: 5 JUN 2013
- Manuscript Accepted: 5 JUN 2013
- Manuscript Received: 14 FEB 2013
- chicken embryo;
- tumor reprogramming
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. Developmental Dynamics 242:1078-1093, 2013. © 2013 Wiley Periodicals, Inc.