Document Detail

Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas.
MedLine Citation:
PMID:  24070417     Owner:  NLM     Status:  In-Data-Review    
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.
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    
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:  -     Revised Date:  -    
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.
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.
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