Brain slice invasion model reveals genes differentially regulated in glioma invasion.
Invasion of tumor cells into adjacent brain areas is one of the major problems in treatment of glioma patients. To identify genes that might contribute to invasion, fluorescent F98 glioma cells were allowed to invade an organotypic brain slice. Gene expression analysis revealed 5 up-regulated and 14 down-regulated genes in invasive glioma cells as compared to non-invasive glioma cells. Two gene products, ferritin and cyclin B1, were verified in human gliomas by immunohistochemistry. Ferritin exhibited high mRNA levels in migratory F98 cells and also showed higher protein expression in the infiltrating edge of human gliomas. Cyclin B1 with high mRNA expression levels in stationary F98 cells showed marked protein expression in the central portions of gliomas. These findings are compatible with the concept of tumor cells either proliferating or migrating. Our study is the first to apply brain slice cultures for the identification of differentially regulated genes in glioma invasion.
Holtkamp
Nikola
N
Institute of Neuropathology, Charité Universitätsmedizin Berlin, Germany. nikola.holtkamp@charite.de
Afanasieva
Anastasia
A
Elstner
Anja
A
van Landeghem
Frank K H
FK
Könneker
Matthias
M
Kuhn
Susanne A
SA
Kettenmann
Helmut
H
von Deimling
Andreas
A
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019926:Cyclin B / Q000096:biosynthesis / Q000235:genetics; D056744:Cyclin B1; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D051381:Rats; D046509:Tissue Culture Techniques
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; C534701:Ccnb1 protein, rat; D019926:Cyclin B; D056744:Cyclin B1; D005293:Ferritins