A RODENT BRAIN ORTHOTOPIC MODEL TO STUDY HUMAN MALIGNANT GLIOMA

作者：Rajcevic Uros^*

来源：Slovenian Veterinary Research, 2011, 48(1): 5-14.

• malignant brain tumors
• glioblastoma
• nude rat
• e-GFP NOD/SCID mice
• xenograft
• orthotopic transplantation
• biopsy spheroids
• translational medicine
• molecular neuro-oncology

Glioblastomas are fatal brain tumors. They have a relatively low incidence, but the fact that regardless of the advances in therapy there hasn't been a major progress in survival over several decades urges the scientists to search for novel diagnostic tools, anti-tumor drug targets and therapies. It appears that our inability to successfully treat brain cancer mostly stems from the lack of understanding of the underlying brain tumor biology. Many rodent orthotopic models have been developed to address issues in drug development as well as biological origins of malignant gliomas. Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. A novel orthotopic rat model of glioblastoma-the most malignant glioma in human-was recently developed, showing some stem-cell properties. The model is based on xenotransplantation of biopsy spheroids from human tumor tissue, into the brain of immunodeficient rats, where they initiated the growth of primary in most cases invasive and angiogenesis-independent glioblastomas. After serial passaging of tumors via spheroids in the subsequent generation of animals, the phenotype of the tumor changed. The most dramatic change was observed in approximately 1/3 of initially invasive tumors that changed into highly angiogenic and very aggressive. Some tumors though, remained invasive even after serial passages, while some were angiogenic from the start. The model thus provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumor progression. In vivo passaging of patient GBM biopsies produced tumors representative of the patient tumors, with high take rates and a reproducible disease course. The model has also been adapted to eGFP expressing immunodeficient mouse in which fluorescently marked tumors can be established in vivo.

• 出版日期2011