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.
Tucker
M A
MA
Brain Tumor Research Laboratories, University of Alabama, Birmingham 35294.
Gillespie
G Y
GY
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