Antigens associated with normal and malignant gastrointestinal tissues

Abstract

Immunization of hamsters with phenol-alcohol extracts of GW-39 human colonic tumor tissues has resulted in the identification of three gastrointestinal tissue-associated antigens, on the basis of precipitin immunoreactivity. Sephadex G-200 and Bio-Gel A-15m chromatography of normal colonic tissue and GW-39 tumor extracts revealed antigen immunoreactivity in the 46,000 (low-molecular-weight), 170,000 to 900,000 (high-molecular-weight), and 5 to 10 million (very high-molecular-weight) ranges or low-molecular-weight colon-specific antigen (LMW/CSA), high-molecular-weight colon-specific antigen (HMW/CSA), and very-high-molecular-weight colon-specific antigen (VHMW/CSA), respectively. Immunodifussion reactions indicated that the HMW/CSA was human gastrointestinal tissue-specific, increasing in concentration from the esophagus to the colon [for which reason the term colon-specific antigen (CSA) has been retained], whereas the LMW/CSA was found in human gastrointestinal tissues, hamster and rat colon, human saliva, and normal human cervix. Colon-specific antigen (CSA) could be demonstrated in human gastrointestinal tumors, including the LS-174T colonic cancer cell line, but not in cancers of other sites tested. Likewise, CSA's were found in fetal human gut tissue. Whereas HMW/CSA and VHMW/CSA showed partial identity in immunodiffusion, HMW/CSA and VHMW/CSA, as well as LMW/CSA and VHMW/CSA, showed distinct immunoprecipitin bands, respectively. The immunoelectrophoretic mobility of VHMW/CSA was similar to an alpha-globulin, whereas HMW/CSA and LMW/CSA migrated to the prealbumin region. CSA appeared in immunofluorescence of GW-39 tumor cells and in the goblet cells of human colon predominantly as a cell-surface component. Staining with periodic acid-Schiff and solubility characteristics of the CSA's suggest that they are glycoprotein in nature. These studies thus support the view that organ-specific and organ-associated antigens of the colon can be maintained and expressed in human colonic carcinomas, including the xenografted GW-39 human colonic tumor system.