PMID- 8316334 OWN - NLM STAT- MEDLINE DCOM- 19930728 LR - 20190920 IS - 0305-1846 (Print) IS - 0305-1846 (Linking) VI - 19 IP - 2 DP - 1993 Apr TI - Secretion of cathepsin B by human gliomas in vitro. PG - 146-51 AB - 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. FAU - McCormick, D AU - McCormick D AD - Neuropathology Laboratory, Queen's University of Belfast. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuropathol Appl Neurobiol JT - Neuropathology and applied neurobiology JID - 7609829 RN - 0 (Cysteine Proteinase Inhibitors) RN - EC 3.4.22.1 (Cathepsin B) RN - EC 3.4.22.2 (Papain) SB - IM MH - Brain Neoplasms/*enzymology MH - Cathepsin B/*metabolism MH - Cysteine Proteinase Inhibitors/metabolism MH - Extracellular Matrix/enzymology MH - Glioma/*enzymology MH - Humans MH - Hydrogen-Ion Concentration MH - Molecular Weight MH - Papain/metabolism MH - Tumor Cells, Cultured EDAT- 1993/04/01 00:00 MHDA- 1993/04/01 00:01 CRDT- 1993/04/01 00:00 PHST- 1993/04/01 00:00 [pubmed] PHST- 1993/04/01 00:01 [medline] PHST- 1993/04/01 00:00 [entrez] AID - 10.1111/j.1365-2990.1993.tb00420.x [doi] PST - ppublish SO - Neuropathol Appl Neurobiol. 1993 Apr;19(2):146-51. doi: 10.1111/j.1365-2990.1993.tb00420.x.