Secretion of cathepsin B by human gliomas in vitro.
There is evidence from investigations of non-CNS neoplasms that secreted proteolytic enzymes may facilitate tumour invasion by partially degrading extracellular matrix (ECM). Among the enzymes which may be involved are members of the cysteine proteinase superfamily and especially cathepsin B (CB). In the present investigation we have studied CB in human gliomas in vitro, concentrating particularly on CB secretion, as extracellular enzyme is of prime importance in this context. We have found that CB is secreted by gliomas in vitro as a latent zymogen, requiring activation. This has been confirmed by gel chromatography which indicated that CB is secreted as a 42 kDa proenzyme which may be proteolytically processed to an enzymatically active 29 kDa molecule. The inactive, high molecular weight, latent CB is stable at extracellular pH in contrast to the activated low molecular weight form which rapidly loses activity at this pH. We have also measured secretion of cysteine proteinase inhibitors (CPI), as their presence would have a direct influence on the effective activity of CB, and found that all of the gliomas secreted significant amounts of a CPI as assessed by papain inhibition. Our experiments suggest that a number of factors are involved in the regulation of extracellular glioma-derived CB activity. These include: rate of secretion of pro-CB, rate of CB activation, destabilization of CB at neutral pH and the presence of cysteine proteinase inhibitors.
McCormick
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Neuropathology Laboratory, Queen's University of Belfast.
D001932:Brain Neoplasms / Q000201:enzymology*; D002401:Cathepsin B / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D005109:Extracellular Matrix / Q000201:enzymology; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D010206:Papain / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D002401:Cathepsin B; D010206:Papain