title: Activation of human platelet-derived latent transforming growth factor-beta 1 by human glioblastoma cells. Comparison with proteolytic and glycosidic enzymes.
abstract: Transforming growth factor-beta (TGF-beta), a regulator of cell growth and differentiation, is secreted by most cultured cells in latent form (L-TGF-beta). Activation of L-TGF-beta can be achieved by various physico-chemical treatments, including acidification, alkalinization, heating and chaotropic agents. Proposed physiological activators include proteinases and glycosidases, which, however, only lead to limited activation (15-20% of the total TGF-beta activity after acidic activation). In the present study L-TGF-beta 1 partially purified from human platelets was not activated by treatment with neuraminidase or the proteinases plasmin, endoproteinase Arg-C, elastase and chymotrypsin. The mechanism of activation of L-TGF-beta was further assessed by using the human glioblastoma cell line 308, which releases biologically active TGF-beta 2. Factor(s) secreted by 308 glioblastoma cells were found to be able to activate partially purified L-TGF-beta 1 from human platelets. Our finding may prove to constitute a physiologically relevant mechanism for the activation of latent forms of TGF-beta in vivo.
authors.affiliation: Department of Internal Medicine, University Hospital of Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Huber
authors.forename: A
authors.initials: A
authors.lastname: Fontana
authors.forename: S
authors.initials: S
authors.lastname: Bodmer
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005910:Glioma; D006801:Humans; D007700:Kinetics; D009439:Neuraminidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D009439:Neuraminidase; D010450:Endopeptidases; D005341:Fibrinolysin