Elevated levels of abnormally-fucosylated haptoglobins in cancer sera

Abstract

Cancer sera have higher levels of serum protein-bound fucose than sera from healthy individuals. In an attempt to identify the cause of this increase, fucoproteins were extracted from the sera of cancer patients and healthy individuals using a fucose-specific lectin (lotus tetragonolobus) coupled to Sepharose, and were analysed by polyacrylamide gel electrophoresis and silver staining. Of the several consistent changes observed for the cancer sera, the most striking was a large increase in a component of 40-45 Kdaltons. The expression of this component in the cancer sera was related to the elevation in serum fucose levels. Two dimensional (2D) electrophoretic analysis of lectin extracts showed that this component had a similar isoelectric point to the beta chains of haptoglobin. Its identity as haptoglobin was confirmed using Western blotting and an anti-haptoglobin antibody. Fucosylated haptoglobins (FHp) were also isolated from some rheumatoid arthritis sera, but there was no correlation between serum fucose levels and the FHp expression. The FHp in cancer sera was of higher molecular weight than that found in rheumatoid sera. Serial specimens from two ovarian cancer patients undergoing chemotherapy had elevated FHp associated with increased amounts of tumour. To the best of our knowledge this is the first time a molecule of this type has been reported in cancer sera and because of its uniqueness it deserves further investigation as a potential cancer marker.