Metabolism of Orthotopic Mouse Brain Tumor Models

Abstract

We used magnetic resonance spectroscopy to determine whether orthotopic mouse brain tumors grown as xenografts in immunocompromised mice either from human brain tumor cells implanted immediately after surgery or from cultured human tumor lines show metabolic profiles comparable to those of the original tumors. Using a 7 T scanner, spectra were acquired from mice with a human atypical teratoid/rhabdoid tumor (AT/RT) either implanted directly from the surgical specimen or first grown in culture, directly implanted choroid plexus carcinoma (CPC), and two medulloblastoma cell lines. The results were compared with spectra from these same tumors or tumor types in patients and with controls. Metabolic variability of tumors from a single cell line was also evaluated using the medulloblastoma lines. The main metabolic features of human tumors were qualitatively replicated in xenografts. AT/RTs in mice exhibited choline, creatine, and myo -inositol levels comparable to those observed in the patient. As in patients, choline was prominent in experimental CPC. Tumors from a single cell line were comparable. Significant correlations were found with key metabolites in humans and mice; however, differences including lower lipids in the implanted AT/RTs than in patient spectra and taurine observed in all animal spectra were also noted. The causes of these dissimilarities warrant further investigation.