Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation.

Abstract

The binding of fluorescein isothiocyanate (FITC)-conjugated lectins to mucin in the human colon was studied by using fluorescence microscopy. In normal mucosa, lectins that preferentially bind to exposed N-acetyl-galactosamine residues (Dolichos biflorus agglutinin and soybean agglutinin) bound selectively to the goblet cell mucin of well-differentiated cells in the upper colonic crypt. By contrast, lectins that require exposed non-reducing galactose residues for binding (Ricinus communis agglutinin1 and Bauhinia purpurea agglutinin) preferentially labeled the mucin of less-differentiated goblet cells located in the lower portion of the colonic crypt. The lectin derived from Arachis hypogaea (peanut agglutinin) has a high affinity for a carbohydrate structure not normally exposed in human tissues. This lectin did not label the goblet cell mucin in the normal colon. However, the mucin was labeled in all 21 colon cancer specimens examined. Additionally, the nonmalignant epithelium immediately adjacent to colon cancer (termed "transitional mucosa") also contained goblet cell mucin that was labeled by FITC-peanut agglutinin. Three conclusions may be drawn from the selective binding characteristics of FITC-lectins to colonic mucins. First, an alteration in the exposed, nonreducing carbohydrate residues occurs in human colonic mucin during the process of goblet cell differentiation. Second, an exposed carbohydrate structure that is not normally present in human tissues is expressed in the mucin produced by malignant colonic epithelium. Third, the presence of the cancer-associated carbohydrate structure in the mucin of transitional mucosa suggests that this tissue may be in the process of early malignant transformation.