Analysis of Tissue Chimerism in Nude Mouse Brain and Abdominal Xenograft Models of Human Glioblastoma Multiforme: What Does It Tell Us About the Models and About Glioblastoma Biology and Therapy?

In situ hybridization coupled to immunohistochemistry for antigens of interest allows unequivocal identification of tumor cells from reactive stroma cells and normal adjacent structures in human glioblastoma multiforme grafts transplanted into nude mice. With this methodology, we have explored the d...

Full description

Saved in:
Bibliographic Details
Published in:The journal of histochemistry and cytochemistry 2000-06, Vol.48 (6), p.847-858
Main Authors: Antunes, Laurent, Angioi-Duprez, Karine S, Bracard, Serge R, Klein-Monhoven, Nathalie A, Le Faou, Alain E, Duprez, Adrien M, Plenat, Francois M
Format: Article
Language:English
Subjects:
Abdominal Neoplasms - pathology
Abdominal Neoplasms - physiopathology
Animals
Brain - pathology
Brain Neoplasms - pathology
Brain Neoplasms - physiopathology
Chimera
Disease Models, Animal
Glioblastoma - pathology
Glioblastoma - physiopathology
Gliosis - pathology
Humans
Mice
Mice, Nude
Neoplasm Transplantation
Transplantation, Heterologous
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In situ hybridization coupled to immunohistochemistry for antigens of interest allows unequivocal identification of tumor cells from reactive stroma cells and normal adjacent structures in human glioblastoma multiforme grafts transplanted into nude mice. With this methodology, we have explored the development of glioblastoma multiforme solid grafts transplanted into nude mouse brains or flanks. The brain transplants closely resembled the human situation, particularly in relation to differentiation and growth patterns. The morphological features of peritumoral reactive gliosis were similar to those observed in humans. A mouse glial stroma within the main tumor masses was also demonstrated. Kinetic studies showed that the compartment of isolated tumor cells that infiltrated host brains and the reactive gliosis constituted two cycling cell populations. Despite VEGF protein expression by tumor cells and some reactive astrocytes, the abnormally permeable microvascular beds were not hyperplastic. The observation of a non-infiltrative pattern of growth when grafts were established in host flanks demonstrated that the organ-specific environment plays a determining role in the growth and invasive properties of glioblastoma. The phylogenetic distance between man and mouse and the recipient immunoincompetence should not impose serious limitations on the use of this model for studying malignant glioma biology and therapy in vivo.
ISSN:0022-1554
1551-5044
DOI:10.1177/002215540004800613