A novel model of intracranial meningioma in mice using luciferase-expressing meningioma cells. Laboratory investigation.
OBJECTIVE
Meningioma research has been hindered by the inability to sequentially measure intracranial tumor growth in a cost-effective, efficient manner. Recently, the luciferase gene has been transfected into cancer lines to obtain cells that express the luciferase enzyme, which oxidizes luciferin in a reaction that releases photon energy that can be measured noninvasively by bioluminescence imaging (BLI) systems. The authors describe a mouse model of intracranial meningioma that uses this novel BLI system.


METHODS
The immortal meningioma cell lines CH-157-MN and IOMM-Lee were transfected with luciferase and neomycin phosphotransferase (LucNeo) and selected with G418. These cells were stereotactically implanted at skull base and cerebral convexity locations in nude mice. Animals were imaged for bioluminescence biweekly, and 5 mice underwent magnetic resonance (MR) imaging. Tumors were harvested for immunohistochemical and ultrastructural analysis.


RESULTS
The CH-157-MN-LucNeo and IOMM-Lee-LucNeo cell lines were successfully implanted intracranially in mice. The tumor induction rate for CH-157-MN-LucNeo skull base tumors was 90% (36 of 40 procedures). Statistical analysis of CH-157-MN-LucNeo skull base tumor volume measured on MR imaging correlated with the results of BLI showed an R value of 0.900. The tumors exhibited characteristics of aggressive meningiomas by insinuating along arachnoid planes and invading brain.


CONCLUSIONS
Noninvasive BLI was successfully used to image intracranial meningiomas in mice. The tumors grew in a fashion similar to that of aggressive meningiomas in humans, and exhibited the microscopic, immunohistochemical, and ultrastructural features characteristic of meningiomas. This animal model overcomes the main obstacle in studying intracranial meningiomas by enabling sequential noninvasive tumor measurement in a cost-effective manner.
Ragel
Brian T
BT
Department of Neurosurgery, University of Utah, Salt Lake City 84132, USA.
Elam
Isaac L
IL
Gillespie
David L
DL
Flynn
Jeannette R
JR
Kelly
David A
DA
Mabey
David
D
Feng
Harvey
H
Couldwell
William T
WT
Jensen
Randy L
RL
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D019868:Kanamycin Kinase / Q000235:genetics; D019394:Ki-67 Antigen / Q000032:analysis; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D049449:Luminescence; D049408:Luminescent Agents / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008579:Meningioma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000032:analysis; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019292:Skull Base Neoplasms / Q000473:pathology; D014162:Transfection; D014183:Transplantation, Heterologous; D014746:Vimentin / Q000032:analysis
D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D049408:Luminescent Agents; D018396:Mucin-1; D014746:Vimentin; D008156:Luciferases; D019868:Kanamycin Kinase