A glycoprotein present in normal human tissue is characterized that is neither organ-nor tumorspecific (nonspecific crossreacting antigen) and that crossreacts (by the Ouchterlony double-diffusion technique) with the carcinoembryonic antigen. This immunological relationship indicates common determinants on the molecules of both antigens. We demonstrate that the nonspecific crossreacting antigen is not a fragment of the carcinoembryonic antigen molecule.In our first publication about the isolation of a fetal antigen from human colonic tumors (1), we mentioned two antigens of B electrophoretic mobility, the carcinoembryonic antigen (CEA) first described by Gold and Freedman (2) and an antigen present in higher amounts in intestinal carcinomas than in noncancerous mucosa that has been found to be a protein present in normal tissues. In the present paper, it will be shown that this latter antigen is neither tumor-nor organspecific. It has been named, therefore, nonspecific crossreacting antigen (NCA). The characterization of NCA and its immunological relationship to CEA is also included in this study. MATERIALS AND METHODSTumor Extracts were prepared from a pool of 15 unpreserved, primary colonic epitheliomas of the glandular type that were removed by surgery and two livers with metastases from the same malignant tumors (obtained at autopsy within 8 hr after death). In this study, only extracts prepared by precipitation of the tissue homogenates with perchloric acid were used, which have a high content of CEA and some other tissue proteins but very little serum proteins.The extraction procedure has been described (1, 3). Semipurified extracts of lung and spleen tissues were also used, as well as purified CEA (3). NCA was obtained (as a byproduct) during isolation of CEA, since it is a constant, tenacious contaminant of the different CEA-purification steps. NCA and CEA were finally separated by consecutive column filtrations on Sephadex G-200 in 0.01 M K-phosphate buffer (pH 8.2).Antisera were prepared in rabbits against semipurified extracts of colonic tumors, normal mucosa, and isolated NCA. An antiserum was also prepared in sheep against purified CEA (3, 4). Precipitation Reactions. Ouchterlony double-diffusion in agar and Scheidegger's modification of immunoelectrophoresis (5) were used, both in 1.5%o agar and 0.15 M veronal-HCl buffer (pH 8.2). RESULTS When the semipurified extract of colonic tumors was further purified by preparative electrophoresis and the cathodic fractions of the extract were analyzed with an antiserum prepared against the semipurified extract by immunoelectrophoresis, two precipitin lines of ( mobility were seen. The inner line represented CEA, and the outer line represented NCA (Fig. 1)
This study concerns the immunohistologic distribution of carcino-embryonic antigen (CEA) in tissues and organs from 86 legal abortions, stillborn fetuses and perinatal deaths and from 5 adults without inflammatory disease or cancer. Monospecific antibodies to CEA of both polyclonal and monoclonal origin were applied to serial sections obtained from formalin-fixed, paraffin-embedded tissue blocks. Starting from the 9th week of gesta-tional age, a positive staining reaction for CEA was found in the surface epithelium of the tongue, the tracheal mucosa and the following locations of the gastro-intestinal tract: the gastro-oesophageal junction, the pyloric antrum, the upper duodenum, throughout the colon and appendix. In the adult, CEA was also found at these sites. All other organs such as the central nervous system, lung, thyroid, thymus, liver, pancreas, gastric corpus, spleen, adrenals, kidney, ureter, bladder, gonads and breast were negative for CEA. Therefore, CEA appears to be a normal antigen in the gastro-intestinal tract at any age from fetal life onwards.
Summary.-Using immunofluorescence methods, 3 antisera respectively stain 3 groups of mucous cells of the human gastrointestinal tract, showing specific antigens for each group of cells.The antigens of the first group, the MI antigens, were principally associated with columnar cells of the gastric epithelium, the M2 antigens with mucous cells of gastric and Brunner's glands, and the M3 antigen with the goblet cells of the intestinal mucosa.The gastric M antigens normally detectable in stomach and duodenum (but not in colon) were expressed in certain colonic tumours (benign or malignant) and in adjacent mucosa. They are always present with the intestinal M3 antigen. In 100 colonic adenocarcinomas, the intestinal M3 antigen was found in 53 cases, gastric Ml antigens in 29 cases, and gastric M2 antigens in 10 cases, always with the two other M antigens. A good correlation could be established between the association of M antigens and the histological type of tumour.
In previous work from this laboratory, extracts of noncancerous human gastric mucosa were studied by immunochemical and electrophoretic means ( 1 ). Gastric mucosal extracts obtained by homogenization at pH 8 were subjected to electrophoresis in agar at pH 8.2. Zones of proteolytic activity at pH 2 were developed directly on the agar by the technique of Uriel (2). Four electrophoretically distinct zones showing proteolytic activity maximal at or near pH 2.0 were found in each of 45 stomachs studied. Thirty-six stomachs were from patients with duodenal ulcer, seven from patients with gastric ulcer, and in two cases, were normal stomachs obtained at autopsy from patients dying of heart disease less than 24 hours before autopsy. These constituents were designated proteases (P) I, II, III, and IV in order of decreasing electrophoretic mobility.Immunoelectrophoretic studies of-gastric mucosal extracts, using antiserum to mucosal extracts, showed three of the proteolytic constituents, P II, III, and IV, to be antigenic and to differ immunochemically from one another (1). These antigens were found in all noncancerous stomachs studied. Preliminary studies of the noninvolved gastric mucosa of 10 patients with gastric carcinoma suggested that the proteolytic constituents were diminished or absent (3). It was thus of considerable interest to define more fully the nature of these gastric mucosal components.The activation of pepsinogen involves the splitting off of basic peptides, resulting in an increased electrophoretic mobility for pepsin.
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