Global Metabolite Profiling of Human Colorectal Cancer Xenografts in Mice Using HPLC–MS/MS

Reversed-phase
gradient LC–MS was used to perform untargeted metabonomic analysis
on extracts of human colorectal cancer (CRC) cell lines (COLO 205,
HT-29, HCT 116 and SW620) subcutaneously implanted into age-matched
athymic nude male mice to study small molecule metabolic profiles
and examine possible correlations with human cancer biopsies. Following
high mass accuracy data analysis using MS and MS/MS, metabolites were
identified by searching against major metabolite databases including
METLIN, MASSBANK, The Human Metabolome Database, PubChem, Biospider,
LipidMaps and KEGG. HT-29 and COLO 205 tumor xenografts showed a distribution
of metabolites that differed from SW620 and HCT 116 xenografts (predominantly
on the basis of relative differences in the amounts of amino acids
and lipids detected). This finding is consistent with NMR-based analysis
of human colorectal tissue, where the metabolite profiles of HT-29
tumors exhibit the greatest similarity to human rectal cancer tissue
with respect to changes in the relative amounts of lipids and choline-containing
compounds. As the metabolic signatures of cancer cells result from
oncogene-directed metabolic reprogramming, the HT-29 xenografts in
mice may prove to be a useful model to further study the tumor microenvironment
and cancer biology.