Comparison of human colonic mucoprotein antigen from normal and neoplastic mucosa.

Colonie mucoprotein antigen (CMA), a high-molecularweight, tissue-specific mucin, was obtained from 9 normal mucosa! samples and 12 colonie adenocarcinomas. Puri fication was achieved by means of phenokwater extrac tion followed by ethanol precipitation and molecular sieve chromatography. Chemical analyses of the individual nor mal 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 W-glycolylneuraminic 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. Alter natively, the possibility exists that the normal colonie mucosa synthesizes more than one mucin and that, as a consequence of neoplasia, one (or more) or these is suppressed or enhanced.