Aberrant regulation favours matriptase proteolysis in neoplastic B-cells that co-express HAI-2

Journal of Enzyme Inhibition and Medicinal Chemistry

Jehng-Kang Wang¹  Yi-Ying Wu²  Yuan Xu³  Chen-Yong Lin³  Robert B. Barndt³  Michael D. Johnson³  Yee Hui Yeo³  Yi-Lin Chiu⁴  Yu-Wen Lin⁴  Bailing Jia⁵  Huan-Cheng Liu⁶  Hou-Ping Sytwo⁷ 

[1] Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan;Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC, USA;Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC, USA;Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan;Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC, USA;Department of Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou, Chin;Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, Washington, DC, USA;Langley High School, McLean, VA, USA;School of Medicine, National Defense Medical Center, Taipei, Taiwan;

关键词: Matriptase;    protease inhibition;    HAI-1;    HAI-2;    B-cell lymphoma;    pericellular proteolytic activity;   

DOI  :  10.1080/14756366.2019.1577831

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY