[Frontiers in Bioscience 16, 2243-2258, June 1, 2011]

Animal models to study cancer-initiating cells from Glioblastoma

Boyoung Wee1, Nikki Charles1,2, Eric C. Holland1,2,3

1Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA,2Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA,3Department of Neurosurgery and Surgery,Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Molecular Pathology
3.1. Cell of origin in glioma formation
3.2. Signaling pathways disrupted in GBMs
4. Cancer stem cells (CSCs)
4.1. Cancer stem cell hypothesis
4.2. Brain tumor-initiating cells (BTICs)
4.3. Specialized microenvironments required for BTICs
5. Animal models to study GBMs & BTICs
5.1. Transplantation models
5.2. Somatic cell gene transfer models
5.3. Transgenic models
5.4. Animal modeling to study BTICs
6. Conclusions: Implications for preclinical testing
7. Acknowledgement
8. References

1. ABSTRACT

Three main subtypes of gliomas with distinct molecular pathologies have been modeled in animals to better understand their biology. Genetically engineered mouse models that take advantage of genetic abnormalities observed in human gliomas have been instrumental in this process. These models better recapitulate signaling transduction pathways and the microenvironment that play crucial roles in glioma formation than in vitro systems or transplantation models. An increasing amount of data supports the existence of cells functionally defined by their self-renewal ability and tumor-initiating potential upon serial transplantation. As the issue of these cells with stem cell character in gliomagenesis becomes more illusive, animal models that provide an accurate experimental system where the stem cell character can be manipulated and studied are urgently needed. This review provides an overview of the current state of the literature with respect to animal models used in the study of gliomas and cells with stem cell character in their native environment.