Immunological analysis of the human tumor cell surface : characterization of polypeptides associated with urinary bladder carcinoma

Abstract: Tumors express antigens characteristic of their malignant phenotype, a fact that has become exploited for the diagnosis of certain types of cancer. As these tumor-associated antigens (TAA) may also provide Information on the molecular mechanisms of tumorogenesls as well as constituting the basis for immunotherapeutlc approaches, much Interest has been focused on the Identification and characterization of TAAs.In the present study we have Investigated the cell surface of human urinary bladder carcinomas (TCC) for the presence of TAAs. Three different approaches were used: 1) lectins of various sugar specificities were employed for the Isolation and comparison of the glycoprotein patterns of different normal and malignant cells, 2) mouse monoclonal antibodies were raised against Intact TCC cells and a large number of hybridomas were searched for tumor-related reactivity, 3) antibody producing B cell cultures from TCC- patients were established by Infection with Epstein Barr virus (EBV).Totally six distinct antigens of protein or glycoprotein nature have 1n this way been Identified as being more or less restricted to TCC cells. Five of these were Identified with mouse monoclonal antibodies and have been subjected to serological analysis against a large number of normal and malignant cell types derived from cell cultures or from fresh tissue Isolates. Although showing a high degree of specificity with both cell lines and tissue the TCC-restr1cted expression was generally more pronounced in the histological samples. Thus, two antigens (plOO and the pl90, pl70 complex) were found on almost all TCC specimens but not on any other cell type tested Including normal uroepithel1um. A third antigen (p92, p23) showed a similar distributional pattern but was to some extent also found on certain normal cells. With the antibody S2C6 an interesting antigenic relationship between TCC tumors and B lymphocytes was revealed. In addition to being selectively expressed by TCC cells the S2C6 antigen (p50) appeared to represent a novel B cell marker of high restriction within the hematopoietic system. Although found on both normal and malignant B cells antigen expression was highly Increased 1n rapidly proliferating B cell cultures suggesting that expression may be growth related. Two other antigens, gp115 Identified by Its affinity for leukoagglutinln and the pl40, p85 complex defined by a mouse monoclonal antibody, have been less well established in terms of tissue type distribution but the available data suggest a close TCC-assoc1at1on also of these molecules.With hopes of finding antibody reactivities reflecting the humoral antitumor response of TCC-patients, a series of EBV-transformed B cell cultures were also established. Although no tumor-related antibodies were found 1n this Initial study the observation that B cell cultures producing antibodies to a variety of cellular antigens could be Isolated from most patients confirms that the method may be of value for the delineation of the Immune response to tumors.In conclusion, the present study has led to the Identification and preliminary characterization of several antigenic components associated with urinary bladder cancer. The restricted distribution of these molecules make them interesting as markers of this disease and their potential use for clinical applications as well as possible Implications 1n tumorogenesis 1s discussed.