Production of a bioactive high molecular weight transforming growth factor beta-like molecule by human malignant glioma cell lines.
The present study describes identification and partial characterization of a glioma-derived high molecular weight transforming growth factor beta-like molecule (HMW-TGF beta) that requires no activation for biological activity. HMW-TGF beta, constitutively produced by the human glioma cell line, D54MG, is not acid- or heat-labile; is relatively resistant to denaturation, reduction, and high salt treatment. Monoclonal antibody 12A12.D7, produced against partially-purified HMW-TGF beta, was used both to deplete and to neutralize directly a > 158 kDa HMW-TGF beta activity from gel filtration fractions; the antibody also directly neutralized purified mature TGF beta 1. 12A12.D7 recognized a single protein species of 186 kDa from unlabeled glioma cell conditioned media and 35S-labeled lysates. HMW-TGF beta is not due to complex formation between TGF beta and any of the known carrier molecules. Production of HMW-TGF beta by glioma cells could facilitate tumor cell proliferation, and thus contribute to the inexorable and rapid progression that characterizes malignant gliomas.
Brain Tumor Research Laboratories, University of Alabama, Birmingham 35294.
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Tucker
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Gillespie
D000906:Antibodies / Q000494:pharmacology; D004586:Electrophoresis / Q000379:methods; D005910:Glioma / Q000737:chemistry* / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D000906:Antibodies; D006131:Growth Inhibitors; D016212:Transforming Growth Factor beta