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(American Journal of Pathology. 2001;159:165-178.)
© 2001 American Society for Investigative Pathology

Regular Articles

Controlling Tumor-Derived and Vascular Endothelial Cell Growth

Role of the 4F2 Cell Surface Antigen

Michael Papetti and Ira M. Herman

From the Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts

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.




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