This project is intended to use immunological and growth factor studies to explore the mechanisms and effects of malignant transformation of bladder epithelium. The goals of these investigations are improved diagnosis, treatment and prevention of transitional cell carcinoma (TCC) in humans. Investigations of tumor associated antigens (TAA) of bladder cancer are being extended by the production of murine hybridomas making monoclonal antibodies to TAA. The antigens defined by these monoclonal antibodies will be characterized in terms of tissue distribution, relationship to oncofetal antigens, presence or absence on normal or inflammatory bladder epithelium, and on other types of malignant cells. TCC-TAA will be further characterized as to their biochemical nature. The consequences of interaction between monoclonal antibodies and cell membrane TAA will be determined to assess both the fate of antigen: antibody complexes and the viability and growth of the cell. The hypothesis that human TCC is characterized by abnormal growth attributable to excessive production of growth factors (GF) and/or inappropriate growth factor receptors (GF-R) will be explored by extending studies that have been initiated on epidermal growth factor (EGF) and EGFR. A TCC-GF that has been identified will be characterized further and new TCC-GF which contribute to TCC growth will be sought. Immunohistological studies of TAA and GF and GF-R will be initiated. In addition, radiolabeled monoclonal antibodies will be utilized in vitro and in nude mouse models to determine those which may serve to localize human TCC in vitro.
