α-L-Fucose: A Potentially Critical Molecule in Pathologic Processes Including Neoplasia

Abstract

A b s t r a c t a-L-Fucose is a 6-carbon deoxyhexose that is commonly incorporated into human glycoproteins and glycolipids. It is found at the terminal or preterminal positions of many cell-surface oligosaccharide ligandsRecent data suggest that the sugar a-L-fucose is essential for the expression of the fully transformed phenotype in many human cell populations. Evidence for such a role comes from studies of common adenocarcinomas and Hodgkin's disease, as well as certain melanomas, neuroblastomas, and leukemias. a-L-Fucose (hereafter denoted as fucose) is not unique or even specific to malignant tissues; in fact, fucose is incorporated into a variety of molecules, not only in humans, but also across the animal kingdom (including bacteria) and in plants. It would seem unlikely that a molecule so widely distributed should have any particular significance in cancer or other pathologic processes. Research concerned with fucose metabolism has been performed using a broad range of biologic sciences, including not only experimental oncology, but also anatomy, embryology, immunopharmacology, glycobiology, cell-adhesion biochemistry, microbiology, parasitology, and plant physiology. The breadth of studies of fucose, combined with the existence of confusing and evolving terminology among these fields, has not been conducive to the dissemination of significant results across disciplinary boundaries.Several years ago a consistent series of intriguing results was reported from the laboratory of Carolyn Mountford, PhD, one of the pioneers in application of nuclear magnetic resonance methods to human oncology. Mountford and colleagues 1 had obtained evidence, in the form of nuclear magnetic resonance spectra from malignant cells and tissues, suggesting that fucose was detectable in these cells but was limited or undetectable in nonmalignant cells from which they were believed to be derived IFigure II.

Isolation and characterization of a fish F-type lectin from gilt head bream (Sparus aurata) serum

“…This suggests that probably each peptide came from the tandem CRDs. In teleost fish, the presence of multiple F-lectin isoforms, such as in A. japonica [16], A. anguilla [18], and M. saxatilis [15], and their inducibility upon inflammatory challenge, together with the observation that fucose and fucose derivatives such as colitose, may be present on the surface of microbial pathogens, suggest a role as recognition factors in innate immune functions [14,19].…”

“…The presence of terminal L-fucose (6-deoxy-L-galactose) as non-reducing terminal residue on various glycoproteins and glycolipids is a key moiety mediating many cellular interactions [14]. Expression of fucose-containing antigens has been observed to dramatically increase during inflammation [14].…”

“…Expression of fucose-containing antigens has been observed to dramatically increase during inflammation [14]. Lectins that recognize fucose have been detected in tissues and fluids of vertebrate and invertebrate species [16].…”

Differential Terminal Fucosylation of N-Linked Glycans Versus Protein O-Fucosylation in Leukocyte Adhesion Deficiency Type II (CDG IIc)

“…The following steps followed the described procedure (39), with slight modifications. A Sephadex G-50 column (30 ϫ 1 cm, mobile phase 50 mM NH 4 ϩ formate ϩ 0.1% SDS ϩ 0.02% NaN 3 ) was used to remove small contaminant molecules. Protein-containing fractions (designed total glycoproteins), to be submitted to analysis of N-and O-linked glycans, were pooled together, and the volume was reduced by lyophilization.…”

“…Alterations in the production of fucosylated glycoconjugates have been observed in development and differentiation, and in pathological conditions as well, including inflammation and tumor progression (1)(2)(3)(4)(5). Disruption of the FX gene, which codes for a key enzyme in fucose metabolism, results in mice that require fucose in their diet for survival, demonstrating the essential nature of fucosylation (6).…”