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Mucin-like Antigens in a Human Pancreatic Cancer Cell Line Identified by Murine Monoclonal Antibodies SPan-1 and YPan-1¹

Gastrointestinal Research Laboratory (151M2), Veterans Administration Medical Center, and Department of Medicine, University of California, San Francisco, California 94121

The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we described the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4–1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive ß-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by bolling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.

¹ This study was supported in part by USPHS Grant CA24321 from the National Cancer Institute and by the Veterans Administration Medical Research Service. Y. S. K. is a Medical Investigator of the Veterans Administration.

² To whom requests for reprints should be addressed, at Gastrointestinal Research Laboratory (151M2), Veterans Administration Medical Center, 4150 Clement St., San Francisco, CA 94121.

Received 3/17/87. Revised 2/19/88. Accepted 4/14/88.