An orthotopic skull base model of malignant meningioma.
Meningioma tumor growth involves the subarachnoid space that contains the cerebrospinal fluid. Modeling tumor growth in this microenvironment has been associated with widespread leptomeningeal dissemination, which is uncharacteristic of human meningiomas. Consequently, survival times and tumor properties are varied, limiting their utility in testing experimental therapies. We report the development and characterization of a reproducible orthotopic skull-base meningioma model in athymic mice using the IOMM-Lee cell line. Localized tumor growth was obtained by using optimal cell densities and matrigel as the implantation medium. Survival times were within a narrow range of 17-21 days. The xenografts grew locally compressing surrounding brain tissue. These tumors had histopathologic characteristics of anaplastic meningiomas including high cellularity, nuclear pleomorphism, cellular pattern loss, necrosis and conspicuous mitosis. Similar to human meningiomas, considerable invasion of the dura and skull and some invasion of adjacent brain along perivascular tracts were observed. The pattern of hypoxia was also similar to human malignant meningiomas. We use bioluminescent imaging to non-invasively monitor the growth of the xenografts and determine the survival benefit from temozolomide treatment. Thus, we describe a malignant meningioma model system that will be useful for investigating the biology of meningiomas and for preclinical assessment of therapeutic agents.
Baia
Gilson S
GS
Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.
Dinca
Eduard B
EB
Ozawa
Tomoko
T
Kimura
Edna T
ET
McDermott
Michael W
MW
James
C David
CD
VandenBerg
Scott R
SR
Lal
Anita
A
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000502:physiology; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D008579:Meningioma / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods*; D019292:Skull Base Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D000077204:Temozolomide; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018906:Antineoplastic Agents, Alkylating; D013778:Tetrazolium Salts; D013844:Thiazoles; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; C022616:thiazolyl blue; D000077204:Temozolomide