Controlling Tumor-Derived and Vascular Endothelial Cell Growth : Role of the 4F2 Cell Surface Antigen

摘要

We have isolated a monoclonal antibody, clone ßE11, 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 ßE11 antigen inhibits their growth in a dose-dependent manner in vitro with maximal inhibition at an antibody concentration of 1 µg/ml. Different tumor cell lines demonstrate varying sensitivities to anti-ßE11 with the following order of growth inhibition: colon > prostate = glioma > melanoma = fibroblast > breast > liver. Furthermore, the ßE11 antigen localizes to regions of prostatic intraductal neoplasia in paraffin-embedded sections. Mass spectrometry of the cell-derived ßE11 protein and V8-protease fingerprint analysis indicate that the ßE11 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 ßE11 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.