Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy

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Abstract
The aim was to determine whether proton magnetic resonance spectroscopy (MRS) could grade human colorectal cells of differing malignant potential. A cell model of tumour development and progression comprising 2 non‐tumorigenic adenoma lines and 4 carcinoma lines of increasing tumorigenicity was chosen. A gradual reduction in cellular differentiation and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One‐dimensional and 2‐dimensional MRS showed that reduced differentiation in the cell model correlated with an increase in the levels of lipid, metabolites, the glycosylation intermediate uridine diphospho‐N‐acetylglucosamine and cell‐surface fucosylation. Mutations involving the K‐ras, APC and DCC genes are present both in adenoma‐ and in carcinoma‐derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomitant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP‐hexose (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and HI at 5.99 ppm) and the appearance of an additional fucosyl resonance (cross peak between‐CH3 at 1.41 and H5 at 4.30 ppm) in the least tumori‐genic of the carcinoma cell lines. An increase in complexity of the fucosylation spectral pattern was observed with further cellular de‐differentiation and increased tumorigenicity. Collectively these data support the existence of an adenoma‐carcinoma sequence.