IDENTIFICATION AND POTENTIAL USE OF A SOLUBLE TUMOR-ANTIGEN FOR THE DETECTION OF LIVER-FLUKE-ASSOCIATED CHOLANGIOCARCINOMA INDUCED IN A HAMSTER MODEL

A liver-fluke-associated cholangiocarcinoma (CCA), comparable to that occurring in humans, was induced by exposing Opisthorchis viverrini-in fected hamsters to dimethylnitrosamine (DMN). Tumor masses were remove d and histopathologically identified, then one portion was extracted f or antigens used in the production of monoclonal antibodies (MAbs). Th e remaining portions were used to establish CCA cell lines. The antige ns produced and secreted by these cell lines, as well sa those origina lly present in the tissue extracts, possessed a 200-kDa glycoprotein t hat appeared to be immunologically distinct from tumor markers. A spec ific MAb called 6E5 was used to set up a sandwich ELISA for the quanti fication of this antigen in the serum bile of tumor-bearing animals. T he assay system was sensitive enough to detect the antigen at concentr ations below 10 ng/ml. The serum and biliary levels of this antigen we re markedly elevated in animals with progressive tumors when compared with untreated controls. The serum taken serially from each animal tha t subsequently developed CCA showed a gradual but significant elevatio n of the antigen as carcinogenesis progressed. A few isolated animals exhibited a slight elevation of the antigen at a time as early as the end of DMN treatment, when the CCA should not yet have developed, judg ing from microscopic examination. The data from this animal model sugg ested that the CCA-associated soluble antigen defined by MAb 6E5 was a useful marker for the detection of tumors at an early stage of develo pment. (C) 1994 Wiley-Liss, Inc.