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Journal of Histochemistry and Cytochemistry, Vol. 48, 847-858, June 2000, Copyright © 2000, The Histochemical Society, Inc.


ARTICLE

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?

Laurent Antunesa, Karine S. Angioi–Duprezc, Serge R. Bracardb, Nathalie A. Klein–Monhovend, Alain E. Le Faoue, Adrien M. Dupreza, and François M. Plénata
a Laboratoire de Pathologie Cellulaire et Moléculaire en Nutrition, EP CNRS 616, Faculté de Médecine Nancy
b Département de Neuroradiologie, Centre Hospitalier Universitaire Nancy
c Service d'Ophtalmologie, Centre Hospitalier Universitaire Nancy
d Laboratoire Commun de Biologie Moléculaire, Centre Hospitalier Universitaire Nancy
e Laboratoire de Virologie, Centre Hospitalier Universitaire Nancy, Nancy, France

Correspondence to: François M. Plénat, Laboratoire de Pathologie Cellulaire et Moléculaire en Nutrition, EP CNRS 616, Faculté de Médecine Nancy, BP 184, 54505 Vandoeuvre Les Nancy Cedex, France. E-mail: plenat@facmed.u-nancy.fr

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. (J Histochem Cytochem 48:847–858, 2000)

Key Words: in situ hybridization, chimerism, glioblastoma multiforme, nude mice


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