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Relationship of Pancreatic Cancer Apomucin to Mammary and Intestinal Apomucins¹

Gastrointestinal Research Laboratory, VA Medical Center and Department of Medicine, School of Medicine, University of California, San Francisco, California 94121 [J. C. B., J. J. L. H., S. B. H., B. S., J. H., P-S. Y., Y. S. K] and Department of Energy Plant Research Laboratory and Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824 [D. T. A. L.]

Pancreatic cancer mucins have several carbohydrate antigens that are potentially useful in the detection of pancreatic cancers, but little is known about the core polypeptides of pancreatic cancer mucins. In this study, purified mucin from SW1990 pancreatic cancer xenografts was deglycosylated by treatment with hydrogen fluoride to give pancreatic cancer apomucin. Consistent with near-complete removal of carbohydrate, the apomucin had 10- to 70-fold decreased binding of lectins and, unlike the native mucin, served as an acceptor for polypeptidyl N-acetylgalactosaminyl transferase. Antibodies prepared against the apomucin did not bind to native mucin, and antibodies that bound to native mucin did not bind to apomucin. On the basis of cross-reaction with deglycosylated colon cancer mucin and intestinal mucin repeat peptide, apomucins from SW1990 pancreatic cancer xenografts contain the intestinal mucin repeat peptide. On the basis of binding of breast cancerreactive monoclonal antibodies 139H2, DF3, and HMFG-2, apomucins from SW1990 pancreatic cancer xenografts also have the mammary mucin repeat peptide. Using complementary DNA probes specific for intestinal mucin and breast mucin sequences, both types of apomucin mRNA were detected in nude mouse xenografts of SW1990 cells. In immunohistochemical staining, antibody against deglycosylated SW1990 mucin stained normal breast and pancreas but not normal colon. Some pancreatic and mammary cancers and most colonic cancers, however, were stained by antibodies against both intestinal apomucin and mammary apomucin. We conclude that pancreatic cancers can produce mucins with the intestinal repeat peptide as well as those with mammary repeat peptide sequences.

¹ This study was supported by the Veterans Administration Medical Research Service (J. C. B., B. S., S. B. H., Y. S. K.), USPHS Grant CA24321 (J. J. L. H., J. C. B., Y. S. K.), and Department of Energy Contract DE-AC 02-76ER01 338 (D. T. A. L.).

Received 6/ 1/90. Accepted 11/16/90.

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