Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy.
Mouse glioma 261 (Gl261) cells are used frequently in experimental glioblastoma therapy; however, no detailed description of the Gl261 tumor model is available. Here we present that Gl261 cells carry point mutations in the K-ras and p53 genes. Basal major histocompatibility complex (MHC)I, but not MHCII, expression was detected in Gl261 cells. The introduction of interferon-gamma-encoding genes increased expression of both MHCI and MHCII. A low amount of B7-1 and B7-2 RNA was detected in wild-type cells, but cytokine production did not change expression levels. Gl261 cells were transduced efficiently by adenoviral vectors; the infectivity of retroviral vectors was limited. Low numbers of transplanted Gl261 cells formed both subcutaneous and intracranial tumors in C57BL/6 mice. The cells were moderately immunogenic: prevaccination of mice with irradiated tumor cells 7 days before intracranial tumor challenge prevented tumor formation in approximately 90% of mice. When vaccination was carried out on the day or 3 days after tumor challenge, no surviving animals could be found. In vitro-growing cells were radiosensitive: less than 2 Gy was required to achieve 50% cell mortality. Local tumor irradiation with 4 Gy X-rays in brain tumor-bearing mice slowed down tumor progression, but none of the mice were cured off the tumor. In conclusion, the Gl261 brain tumor model might be efficiently used to study the antitumor effects of various therapeutic modalities, but the moderate immunogenicity of the cells should be considered.
Szatmári
Tünde
T
Department of Molecular and Tumor Radiobiology, Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest 1221, Hungary.
Lumniczky
Katalin
K
Désaknai
Szilvia
S
Trajcevski
Stéphane
S
Hídvégi
Egon J
EJ
Hamada
Hirofumi
H
Sáfrány
Géza
G
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor / Q000502:physiology* / Q000528:radiation effects; D004195:Disease Models, Animal; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011836:Radiation Tolerance; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D006649:Histocompatibility Antigens; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53