Magnetic Resonance Spectroscopy detects alterations to the plasma membrane and cell surface which occur in premalignant and malignant cells. Two such changes are the formation of neutral lipid domains in the plasma membrane and fucosylation of cell surface molecules. It has also been observed that lipid vesicles are spontaneously shed from the plasma membranes of some malignant cells and there is evidence to suggest that they may have a functional role in cancer metastasis. It is proposed to test the following hypotheses: The lipid composition of the plasma membrane influences the rate of shedding of plasma membrane vesicles'. 'Plasma membrane vesicles can temporarily transfer some cell surface properties to other cells (specifically degree of fucosylation). The following experiments will be undertaken: Compare the chemical composition of the plasma membranes isolated from: (a) A series of rat mammary adenocarcinoma cell lines with varying metastatic potential. The non-metastatic and highly metastatic cell lines have already extensively characterised in this laboratory. (b) Human colonic polyp and human colon cancers of varying degrees of tumorigenicity. * Isolate, quantify and characterise any lipid vesicles shed by these cell lines. * Attempt to transfer cell surface properties by the incorporation of vesicles from one cell line into another. * Investigate the possibility which promote metastatic capacity in vivo using the rat mammary adenocarcinoma metastasis model. The long term objectives of this group are to document the chemical changes which are measurable by magnetic resonance methods during tumor development from early stages of colonic polyps. This information is imperative for the optimal usage of magnetic resonance imaging and spectroscopy for the detection of colon cancer in humans.
| Mackinnon, W B; Huschtscha, L; Dent, K et al. (1994) Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy. Int J Cancer 59:248-61 |
| Lean, C L; Mackinnon, W B; Delikatny, E J et al. (1992) Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. Biochemistry 31:11095-105 |
| Mackinnon, W B; Hancock, R; Dyne, M et al. (1992) Evaluation of an in vitro invasion assay for use on solid tissue samples and cultured cells. Invasion Metastasis 12:241-52 |
| Lean, C L; Mackinnon, W B; Mountford, C E (1991) Fucose in 1H COSY spectra of plasma membrane fragments shed from human malignant colorectal cells. Magn Reson Med 20:306-11 |
