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.
Papetti
M
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Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Herman
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IM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D027261:Fusion Regulatory Protein-1; D006031:Glycosylation; D008938:Mitosis / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D014018:Tissue Distribution
D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; C431425:betaE11 antigen, bovine