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Comparison of Human Colonic Mucoprotein Antigen from Normal and Neoplastic Mucosa¹

Department of Pathology, Health Sciences Center, State University of New York, at Stony Brook, Stony Brook, New York 11794

Colonic mucoprotein antigen (CMA), a high-molecularweight, tissue-specific mucin, was obtained from 9 normal mucosal samples and 12 colonic adenocarcinomas. Purification was achieved by means of phenol:water extraction followed by ethanol precipitation and molecular sieve chromatography. Chemical analyses of the individual normal CMA preparations indicated similar qualitative and quantitative compositions. The peptide portion of the molecule was characterized by a high content of threonine, serine, proline, glutamic acid, and glycine. The oligosaccharide chains were composed of N-glycolyineuraminic acid, fucose, galactose, glucosamine, and galactosamine. A comparison of the normal and tumor CMA revealed the following differences. Although the amino acid compositions were similar, tumor CMA's had 40% less threonine and 40% more aspartic acid than did CMA's from normal tissue. Both observations were statistically significant at 2 p < 0.001. Normal and tumoral mucins could be distinguished by the aspartate:threonine ratio with a confidence of greater than 99.9%. A 2-fold increase in molar ratio of sialic acid:threonine in tumor-derived CMA was detected (2p < 0.05). These differences suggest that tumor CMA has a lower density of carbohydrate moieties on the peptide core. Tumor CMA may arise by the expression of a new or altered DNA sequence. Alternatively, the possibility exists that the normal colonic mucosa synthesizes more than one mucin and that, as a consequence of neoplasia, one (or more) or these is suppressed or enhanced.

¹ Supported by USPHS Grant CA-17518 and partially by Grant CA-21930 from the National Cancer Institute, NIH.

² Recipient of a USPHS Postdoctoral Fellowship under Training Grant CA-09121 from the National Cancer Institute, NIH. Dr. Gold is currently in the Dept. of Path., Univ. of Kentucky, Lexington, Ky. 40506. Queries to Dr. Miller.

Received 12/19/77. Accepted 6/20/78.