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J Enzyme Inhib Med Chem ; 34(1): 692-702, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30777474

RESUMO

Matriptase is ectopically expressed in neoplastic B-cells, in which matriptase activity is enhanced by negligible expression of its endogenous inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. HAI-1, however, is also involved in matriptase synthesis and intracellular trafficking. The lack of HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed. Here, we show that HAI-2 is commonly co-expressed in matriptase-expressing neoplastic B-cells. The level of active matriptase shed after induction of matriptase zymogen activation in 7 different neoplastic B-cells was next determined and characterised. Our data reveal that active matriptase can only be generated and shed by those cells able to activate matriptase and in a rough correlation with the levels of matriptase protein. While HAI-2 can potently inhibit matriptase, the levels of active matriptase are not proportionally suppressed in those cells with high HAI-2. Our survey suggests that matriptase proteolysis might aberrantly remain high in neoplastic B-cells regardless of the levels of HAI-2.


Assuntos
Linfócitos B/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicoproteínas de Membrana/biossíntese , Proteólise/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Humanos , Glicoproteínas de Membrana/metabolismo , Serina Endopeptidases/biossíntese
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