Document Detail


Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas.
MedLine Citation:
PMID:  24070417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Membrane-associated serine protease matriptase is widely expressed by epithelial/carcinoma cells in which its proteolytic activity is tightly controlled by the Kunitz-type protease inhibitor, hepatocyte growth factor activator inhibitor (HAI-1). We demonstrate that, although matriptase is not expressed in lymphoid hyperplasia, roughly half of the non-Hodgkin B-cell lymphomas analyzed express significant amounts of matriptase. Furthermore, a significant proportion of these tumors express matriptase in the absence of HAI-1. Aggressive Burkitt lymphoma was more likely than indolent follicular lymphoma to express matriptase alone (86% versus 36%). In the absence of significant HAI-1 expression, the lymphoma cells activate and shed active matriptase when the cells are stimulated with mildly acidic buffer or the hypoxia-mimicking agent, CoCl2. The shed active matriptase can initiate pericellular proteolytic cascades by activating urokinase-type plasminogen activator on the cell surface of monocytes, and it can activate prohepatocyte growth factor. In addition, matriptase knockdown suppressed proliferation and colony-forming ability of neoplastic B cells in culture and growth as tumor xenografts in mice. Furthermore, exogenous expression of HAI-1 significantly suppressed proliferation of neoplastic B cells. These studies suggest that dysregulated pericellular proteolysis as a result of unregulated matriptase expression with limited HAI-1 may contribute to the pathological characteristics of several human B-cell lymphomas through modulation of the tumor microenvironment and enhanced tumor growth.
Authors:
Feng-Pai Chou; Ya-Wen Chen; Xianfeng F Zhao; Zijun Y Xu-Monette; Ken H Young; Ronald B Gartenhaus; Jehng-Kang Wang; Hiroaki Kataoka; Annie H Zuo; Robert J Barndt; Michael Johnson; Chen-Yong Lin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  183     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2013 Oct 
Date Detail:
Created Date:  2013-09-27     Completed Date:  2014-04-22     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1306-17     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / enzymology,  pathology
Cell Line, Tumor
Cell Proliferation
Female
Hepatocyte Growth Factor / metabolism
Humans
Lymph Nodes / enzymology,  pathology
Lymphoma, B-Cell / enzymology*,  pathology*
Mice
Mice, SCID
Proteinase Inhibitory Proteins, Secretory / metabolism
Proteolysis*
Serine Endopeptidases / metabolism*
Urokinase-Type Plasminogen Activator / metabolism
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
P30-CA051008/CA/NCI NIH HHS; R01 CA 123223/CA/NCI NIH HHS; R01 CA123223/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proteinase Inhibitory Proteins, Secretory; 0/SPINT1 protein, human; 67256-21-7/Hepatocyte Growth Factor; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/matriptase; EC 3.4.21.73/Urokinase-Type Plasminogen Activator
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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