Document Detail


Laminin-332 cleavage by matriptase alters motility parameters of prostate cancer cells.
MedLine Citation:
PMID:  20672321     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Matriptase, a type II transmembrane serine protease, has been linked to initiation and promotion of epidermal carcinogenesis in a murine model, suggesting that deregulation of its role in epithelia contributes to transformation. In human prostate cancer, matriptase expression correlates with progression. It is therefore of interest to determine how matriptase may contribute to epithelial neoplastic progression. One approach for studying this is to identify potential matriptase substrates involved in epithelial integrity and/or transformation like the extracellular matrix macromolecule, laminin-332 (Ln-332), which is found in the basement membrane of many epithelia, including prostate. Proteolytic processing of Ln-332 regulates cell motility of both normal and transformed cells, which has implications in cancer progression.
METHODS: In vitro cleavage experiments were performed with purified Ln-332 protein and matriptase. Western blotting, enzyme inhibition assays, and mass spectrometry were used to confirm cleavage events. Matriptase overexpressing LNCaP prostate cancer cells were generated and included in Transwell migration assays and single cell motility assays, along with other prostate cells.
RESULTS: We report that matriptase proteolytically cleaves Ln-332 in the β3 chain. Substrate specificity was confirmed by blocking cleavage with the matriptase inhibitor, Kunitz domain-1. Transwell migration assays showed that DU145 cell motility was significantly enhanced when plated on matriptase-cleaved Ln-332. Similarly, Transwell migration of matriptase-overexpressing LNCaP cells was significantly increased on Ln-332 and, as determined by live single-cell microscopy, two motility parameters of this cell line, speed and directional persistence, were also higher.
CONCLUSIONS: Proteolytic processing of Ln-332 by matriptase enhances speed and directional persistence of prostate cancer cells.
Authors:
Manisha Tripathi; Alka A Potdar; Hironobu Yamashita; Brandy Weidow; Peter T Cummings; Daniel Kirchhofer; Vito Quaranta
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 Prostate     Volume:  71     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-24     Completed Date:  2011-01-24     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  184-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Affiliation:
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Cell Movement / physiology*
Humans
Laminin / metabolism*
Male
Microscopy, Phase-Contrast
Prostatic Neoplasms / enzymology,  metabolism*,  pathology
Proteinase Inhibitory Proteins, Secretory / pharmacology
Serine Endopeptidases / metabolism*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Grant Support
ID/Acronym/Agency:
CA47858-17A2/CA/NCI NIH HHS; GM067221-03/GM/NIGMS NIH HHS; R01 CA047858/CA/NCI NIH HHS; U54 CA113007/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Laminin; 0/Proteinase Inhibitory Proteins, Secretory; 0/SPINT1 protein, human; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/matriptase
Comments/Corrections

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


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