Glycomics

See Also

• Thomsen-Friedenreich (T-Tn) antigen
• 'A-Like' tumor antigens

Description

The Forssman antigen, also known as globopentosylceramide, is a glycolipid structure formed by the addition of GalNAc in alpha1-3 linkage to the terminal GalNAc residue of globoside. There is also evidence in the literature that Forssman-specific monoclonal antibodies can detect Forssman-reactive glycoproteins, but the nature of these molecules is not known.

Discussion

The Forssman antigen molecule is expressed during embryonic and adult life in rodents and other mammals, but uncertainty exists about the ability of humans to express this antigen. For example, there is evidence that humans maintain moderate titers of naturally occurring anti-Forssman antibodies in plasma, suggesting that humans do not express the Forssman antigen. In contrast, there is evidence that such antibodies are not consistently present in humans and that when generated, may contribute to the pathogenesis of the Guillain-Barre syndrome by binding to glycolipid components of peripheral nerve myelin.

Similarly, evidence exists that small amounts of Forssman reactivity may be found on human gastrointestinal epithelium, by various human cultured cell lines, by pulmonary and gastointestinal tract carcinomas. These conflicting observations may be a reflection of varied specificities of the anti-Forssman monoclonal antibodies used by different investigators and by differences in epitope reactivity achieved with immunohistochemical procedures versus thin-layer chromatography/antibody overlay procedures. The function of this antigen is not known.

The ability of anti-Forssman antibodies to disrupt tight junction formation, apical-basal polarization, and adhesion suggests that this molecule may participate in cell-cell adhesion and communication processes. The mechanisms that account for these observations are not defined, nor are there corollary studies that have confirmed these observations in a more physiological context.

Abstracts

Isoantigenic expression of Forssman glycolipid in human gastric and colonic mucosa: Its possible identity with “A-like antigen” in human cancer

Proc Natl Acad Sci U S A. 1977 July; 74(7): 3023–3027.

S. Hakomori, S.-M. Wang, and W. W. Young, Jr.

• The heterogenetic Forssman antigen is a glycosphingolipid, a ceramide pentasaccharide with the structure GalNAcα1→3GalNAcβ1→3Galα1→4Galβ1→4Glc→ceramide. Forssman-positive animals are capable of synthesizing this compound in tissues or in erythrocytes, in contrast to the Forssman-negative species, including humans, which are incapable of adding the last carbohydrate in the sequence of the Forssman antigen, namely αGalNAc. The Forssman glycolipid and its precursor globoside were examined in twenty-one samples of surgically extirpated gastrointestinal mucosa and tumors derived therefrom. The results revealed that a few patients had chemically and immunologically detectable levels of the Forssman glycolipid as a normal component of their gastrointestinal mucosa (F+ population); in contrast, the majority of patients did not contain this glycolipid in their normal mucosa (F- population). Whereas the F- population included blood groups A, B, and O, the F+ population did not correspond to blood group A. The Forssman status in tumors taken from the F+ or F- population showed the following striking features: (i) all tumors derived from F- mucosa possessed Forssman glycolipid, whereas (ii) none of the tumors originating in F+ mucosa contained Forssman glycolipid. Globoside, the immediate precursor of Forssman antigen, was distributed equally among F+ and F- mucosa and the tumors derived therefrom. Thus, the expression of Forssman antigen in gastrointestinal mucosa appears akin to that of an isoantigen. Furthermore, the Forssman antigen that appears in tumors of the F- population could represent a human tumor-associated antigen. In view of the strong crossreactivity of Forssman antigen with blood group A determinants, the appearance of Forssman antigen in human tumors could be related to the “A-like antigen” (or “neo-A antigen”) of human tumors reported previously