IDENTIFICATION OF FREE DEAMINATED SIALIC-ACID (2-KETO-3-DEOXY-D-GLYCERO-D-GALACTO-NONONIC ACID) IN HUMAN RED-BLOOD-CELLS AND ITS ELEVATED EXPRESSION IN FETAL CORD RED-BLOOD-CELLS AND OVARIAN-CANCER CELLS

Chemical studies have shown the occurrence of the deaminated sialic ac id 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN) in paired sam ples of blood obtained from mothers and newborns of healthy human indi viduals. Most of the KDN was found in red blood cells, although low le vels were detected in mononuclear cells. No N-glycolylneuraminic acid was detected. Unexpectedly, nearly all of the KDN in fetal cord and ma tched maternal red blood cells was present as the free sugar and compa ratively little occurred conjugated or as cytidine 5'-KDN phosphate, T he amount of free KDN in fetal newborn red blood cells was 2.4-fold hi gher than in red blood cells from the mothers or from healthy nonpregn ant women. Free KDN was also identified in normal human ovaries, in ov arian tumors, and in ascites cells obtained from ovarian cancer patien ts. Importantly, as in fetal cord red blood cells, a distinguishing fe ature of KDN expression in ovarian tumor cells was an elevated level o f free KDN compared with normal controls. A positive correlation was f ound between an increase in the ratio of free KDN/N-acetylneuraminic a cid in ovarian adenocarcinomas and the stage of malignancy. This was p articularly evident in tumor cells isolated from the ascites fluid. Th e central importance of these new findings is a-fold. First, they show that free KDN is a minor but ubiquitous sialic acid in human red bloo d cells and that its elevated expression in red blood cells from fetal cord blood compared with maternal red blood cells may be developmenta lly related to blood cell formation during embryogenesis, Second, the enhanced expression of KDN in ovarian cancer cells suggests that this sialic acid, like the alpha 2,8-linked polysialic acid glycotope, may be an oncofetal antigen in these tumors and thus could be an ''early w arning'' signal for onset of disease and/or a marker for detection of recurrence of disease. These new findings highlight the importance of elucidating the role that KDN and KDN-containing glycoconjugates may p lay in normal development and malignancy.