N-Glycolylneuraminic acid in human tumours

Abstract

N-Glycolylneuraminic acid (Neu5Gc) is an abundant sialic acid, occurring in the glycoconjugates of most deuterostome animals. Homo sapiens is a notable exception, since Neu5Gc is effectively absent from normal human tissues. This is due to a deletion in the human gene coding for CMP-Neu5Ac hydroxylase, the enzyme usually responsible for Neu5Gc biosynthesis. Despite this mutation, persistent reports in the literature suggest that Neu5Gc occurs in the glycoconjugates of many human tumours, where it might be responsible for the formation of so-called Hanganutziu-Deicher antibodies. However, the variety of systems studied and the various experimental approaches adopted have yielded a complex picture of Neu5Gc occurrence in human neoplasias. The aim of this paper is therefore to provide a critical review of the evidence for Neu5Gc in human tumours, paying particular attention to the analytical methods employed. The possible clinical applications of Neu5Gc-containing glycoconjugates and Hanganutziu-Deicher antibodies in the diagnosis and treatment of breast cancer and melanoma are also discussed. In view of the lack of CMP-Neu5Ac hydroxylase in human cells, alternative metabolic pathways for the biosynthesis of glycoconjugate-bound Neu5Gc are considered.