Accessing key steps of human tumor progression in vivo by using an avian embryo model.
Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening.
Hagedorn
Martin
M
Institut National de la Santé et de la Recherche Médicale E0113, Molecular Mechanisms of Angiogenesis, University Bordeaux I, Avenue des Facultés, 33405 Talence, France. m.hagedorn@angio.u-bordeaux1.fr
Javerzat
Sophie
S
Gilges
Delphine
D
Meyre
Aurélie
A
de Lafarge
Benjamin
B
Eichmann
Anne
A
Bikfalvi
Andreas
A
D000818:Animals; D001549:Benzamides; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo / Q000166:cytology*; D017931:DNA Primers; D004195:Disease Models, Animal; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D017403:In Situ Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011743:Pyrimidines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D001549:Benzamides; D017931:DNA Primers; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2