Cellular lipid changes in cancer

Cells express a number of carbohydrate and lipid derivatives on their surfaces. Amongst these are glycosphingolipids, which are involved in cellular recognition, cell adhesion and regulation of cell growth. In 1968 the Japanese biochemist Hakomori observed that transformed tissues (i.e. cancer cells) expressed variant forms of glycosphingolipids, often in larger amounts than normal. These glyco-sphingolipids may play a role in the uncontrolled cell growth of cancer. There are characteristic changes in glycosphingolipids in different cancers. In general, there is a reduction in the more complex glycosphingolipids and an over-expression of some of the more unusual glycosphingolipids that may normally only be present in trace amounts.

The more complex glycosphingolipids act as cell-surface antigens; that is, they may be recognized by specific antibodies. The blood group antigens, which cause an immune reaction if blood of one group is infused into someone of another blood group, are of this type. These cell-surface antigens are released to some extent into the circulation and may therefore provide a means of diagnosis of particular cancers. Equally exciting is the idea that specific antibodies against these antigens might be used to target drugs to the cancer cells. Either drugs could be coupled to the antibodies, or the presence of the antigens might be used as the basis for development of a specific vaccine. These ideas have been promoted consistently by Hakomori, who is still very active in the field. Amongst Hakomori's suggestions is the idea that the glycosphingolipids of cancer cells are involved in tumour cell adhesion and in signal transduction, and that it may be possible to develop therapeutic agents that disrupt adhesion ('anti-adhesion therapy') or normalize signalling pathways ('ortho-signalling therapy'). Although trials in cell culture have demonstrated the possibility of antibody-directed tumour killing, these ideas have yet to be developed to a clinically useful stage.

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