title: Development of luciferase tagged brain tumour models in mice for chemotherapy intervention studies.
abstract: The blood-brain barrier (BBB) is considered one of the major causes for the low efficacy of cytotoxic compounds against primary brain tumours. The aim of this study was to develop intracranial tumour models in mice featuring intact or locally disrupted BBB properties, which can be used in testing chemotherapy against brain tumours. These tumours were established by intracranial injection of suspensions of different tumour cell lines. All cell lines had been transfected with luciferase to allow non-invasive imaging of tumour development using a super-cooled CCD-camera. Following their implantation, tumours developed which displayed the infiltrative, invasive or expansive growth patterns that are also found in primary brain cancer or brain metastases. Contrast-enhanced magnetic resonance imaging showed that the Mel57, K1735Br2 and RG-2 lesions grow without disruption of the BBB, whereas the BBB was leaky in the U87MG and VEGF-A-transfected Mel57 lesions. This was confirmed by immunohistochemistry. Bioluminescence measurements allowed the visualisation of tumour burden already within 4 days after injection of the tumour cells. The applicability of our models for performing efficacy studies was demonstrated in an experiment using temozolomide as study drug. In conclusion, we have developed experimental brain tumour models with partly disrupted, or completely intact BBB properties. In vivo imaging by luciferase allows convenient follow-up of tumour growth and these models will be useful for chemotherapeutic intervention studies.
authors.affiliation: Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Kemper
authors.forename: W
authors.initials: W
authors.lastname: Leenders
authors.forename: B
authors.initials: B
authors.lastname: Küsters
authors.forename: S
authors.initials: S
authors.lastname: Lyons
authors.forename: T
authors.initials: T
authors.lastname: Buckle
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: W
authors.initials: W
authors.lastname: Boogerd
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: O
authors.initials: O
authors.lastname: van Tellingen
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003287:Contrast Media; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D019786:Gadolinium DTPA; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism*; D049449:Luminescence; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003287:Contrast Media; D003606:Dacarbazine; D008156:Luciferases; D019786:Gadolinium DTPA; D000077204:Temozolomide