Malignant Astrocytomas Originate from Neural Stem/Progenitor Cells in a Somatic Tumor Suppressor Mouse Model

Sheila Alcantara Llaguno, Jian Chen, Chang Hyuk Kwon, Erica L. Jackson, Yanjiao Li, Dennis K. Burns, Arturo Alvarez-Buylla, Luis F. Parada

Research output: Contribution to journalArticle

405 Scopus citations

Abstract

Malignant astrocytomas are infiltrative and incurable brain tumors. Despite profound therapeutic implications, the identity of the cell (or cells) of origin has not been rigorously determined. We previously reported mouse models based on conditional inactivation of the human astrocytoma-relevant tumor suppressors p53, Nf1, and Pten, wherein through somatic loss of heterozygosity, mutant mice develop tumors with 100% penetrance. In the present study, we show that tumor suppressor inactivation in neural stem/progenitor cells is both necessary and sufficient to induce astrocytoma formation. We demonstrate in vivo that transformed cells and their progeny undergo infiltration and multilineage differentiation during tumorigenesis. Tumor suppressor heterozygous neural stem/progenitor cultures from presymptomatic mice show aberrant growth advantage and altered differentiation, thus identifying a pretumorigenic cell population.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalCancer Cell
Volume15
Issue number1
DOIs
StatePublished - Jan 6 2009

Keywords

  • CELLCYCLE
  • STEMCELL

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Alcantara Llaguno, S., Chen, J., Kwon, C. H., Jackson, E. L., Li, Y., Burns, D. K., Alvarez-Buylla, A., & Parada, L. F. (2009). Malignant Astrocytomas Originate from Neural Stem/Progenitor Cells in a Somatic Tumor Suppressor Mouse Model. Cancer Cell, 15(1), 45-56. https://doi.org/10.1016/j.ccr.2008.12.006