Characterization of orthotopic glioblastoma xenografts in GFP expressing mice and comparison with rat xenografts. (Doctoral thesis)
- NORLUX Neuro-Oncology Laboratory
The aim of the thesis was to develop and characterize a new patient derived xenograft model in Green Fluorescent Protein (GFP) expressing mice in order to develop a new tool to study tumor - host cellular interactions in human Glioblastomas (GBMs). The thesis is divided into five chapters.
Chapter one constitutes the introduction to the experimental work. It provides a brief introduction to cancer research followed by a description of tumors of the Central Nervous System (CNS), with a particular focus on GBMs. Since this thesis deals with tumor angiogenesis and to some extent with tumor - host interactions, a focus has also been given to physiological and pathological angiogenesis. Finally, since this work describes a new animal model for human GBMs, a section is included focusing on animal models as a tool to study brain tumor initiation and progression.
In chapter two, the aims of the thesis are described. The third chapter is dedicated to experimental procedures (materials and methods).
The main results are presented in chapter four. Since human GBMs are usually xenografted into the CNS of both immunodeficient mice and rats, we performed a comparative study focusing on the tumor growth patterns in the two species, with special reference to infiltrative and angiogenic growth. As a way to study tumor - host interactions, an important part is also dedicated to the effect of stromal cells on tumor properties in vitro. Since many experiments were performed in GFP expressing immunedeficient mice we also studied putative cell-fusion phenomena between tumor and host cells.
Chapter five represents a general discussion, representing a critical analysis of the results obtained, remaining questions and followed by a section on future perspectives of this work.