Controlling tumor-derived and vascular endothelial cell growth: role of the 4Ff2 cell surface antigen

We have isolated a monoclonal antibody, clone betaE11, which recognizes an antigen that is highly abundant on the surface of mitotic vascular endothelial cells and tumor cells. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, expression of this 190-kd antigen is approximately threefold higher in mitotic versus interphase endothelial cells. Treatment of tumor cells with an antibody to the betaE11 antigen inhibits their growth in a dose-dependent manner in vitro with maximal inhibition at an antibody concentration of 1 microg/ml. Different tumor cell lines demonstrate varying sensitivities to anti-betaE11 with the following order of growth inhibition: colon > prostate = glioma > melanoma = fibroblast > breast > liver. Furthermore, the betaE11 antigen localizes to regions of prostatic intraductal neoplasia in paraffin-embedded sections. Mass spectrometry of the cell-derived betaE11 protein and V8-protease fingerprint analysis indicate that the betaE11 antigen is nearly identical to the 4F2 heavy chain antigen, a cell surface protein that has been implicated in cell activation and proliferation. Expression of the betaE11 antigen during mitosis functionally links it to a fundamental aspect of cell proliferation, and its spatial localization on the surface of both proliferating endothelium and tumor cells demonstrates its potential for tumor immunotherapy.