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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2008 Dec 30

PMID 19111880

Citations 369

Authors

Sheila Alcantara Llaguno

Jian Chen

Chang-Hyuk Kwon

Erica L Jackson

Yanjiao Li

Dennis K Burns

Arturo Alvarez-Buylla

Luis F Parada

Affiliations

Soon will be listed here.

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.

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