Controlling tumor-derived and vascular endothelial cell growth - Role of the 4F2 cell surface antigen

We have isolated a monoclonal antibody, clone beta E11, which recognizes an antigen that is highly abundant on the surface of mitotic vascular endothe lial cells and tumor cells. By sodium dodecyl sulfate-polyacrylamide gel el ectrophoresis and Western blotting, expression of this 190-kd antigen is ap proximately threefold higher in mitotic versus interphase endothelial cells . Treatment of tumor cells with an antibody to the beta EI1 antigen inhibit s their growth in a dose-dependent manner in vitro with maximal inhibition at an antibody concentration of 1 mug/ml. Different tumor cell lines demons trate varying sensitivities to anti-beta E11 with the following order of gr owth inhibition: colon > prostate = glioma > melanoma = fibroblast > breast > liver. Furthermore, the beta E11 antigen localizes to regions of prostat ic intraductal neoplasia in paraffin-embedded sections. Mass spectrometry o f the cell-derived beta E11 protein and V8-protease fingerprint analysis in dicate that the beta E11 antigen is nearly identical to the 4F2 heavy chain antigen, a cell surface protein that has been implicated In cell activatio n and proliferation. Expression of the beta E11 antigen during mitosis func tionally links it to a fundamental aspect of cell proliferation, and its sp atial localization on the surface of both proliferating endothelium and tum or cells demonstrates its potential for tumor immunotherapy.