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A New Mucin-associated Oncofetal Antigen, a Marker of Early Carcinogenesis in Rat Colon¹

Laboratoire d'Immunochimie, ER 277 CNRS, I.R.S.C., B. P. 8, 94802 Villejuif Cédex [C. D., R. G., J. B., P. B.]; C.H.U., Amiens [N. D.]; and Institut d'Immunobiologie, Hôpital Broussais, 96 rue Didot, 75014 Paris [J. L. P.], France

We report the characterization of an IgG2a monoclonal antibody, (MAb) 660, prepared against rat gastric high molecular weight glycoproteins. By immunoperoxidase staining, MAb 660 reacted only with the mucous cells of surface gastric epithelium and with a few duodenal goblet cells close to the pylorus in normal adult rats. In fetuses, it reacted with intestinal and colonic goblet cells. The adult colon was always negative. The MAb 660 stained 100% (30 of 30) of chemically induced colonic carcinomas and 100% (7 of 7) of duodenal carcinomas. Several weeks before the appearance of tumors, histologically normal glands, then hyperplasia and dysplasia were precociously stained with MAb 660. The tissue distribution was different from that of blood group related antigens and M1 fucomucins. The recognized antigen was not sensitive to neuraminidase treatment.

After electrophoresis in polyacrylamide gel, staining with periodic acid-Schiff reagent and Western blotting showed that the MAb 660 recognized an epitope associated with high molecular weight glycoproteins. This epitope was unaffected by ß-mercaptoethanol reduction-periodate treatment and neuraminidase and trypsin digestion. However, trypsin digestion performed after ß-mercaptoethanol reduction destroyed the 660 epitope. These data suggest that the antibody could recognize the peptide moiety of the mucin rather than its carbohydrate moiety.

Thus, the new antigen identified by MAb 660 is a mucin-type glycoprotein with an oncofetal behavior in the rat colon and is precociously expressed by precancerous colonic mucosa.

¹ This work was supported by Grant 508138 from the Caisse Nationale de l'Assurance Maladie des Travailleurs Salairés.

² To whom requests for reprints should be addressed.

Received 7/10/87. Revised 11/12/87. Accepted 11/30/87.