Document Detail

Clathrin pit-mediated endocytosis of neutrophil elastase and cathepsin G by cancer cells.
MedLine Citation:
PMID:  22915586     Owner:  NLM     Status:  MEDLINE    
Neutrophil elastase (NE) is a neutrophil-derived serine proteinase with broad substrate specificity. We have recently demonstrated that NE is capable of entering tumor cell endosomes and processing novel intracellular substrates. In the current study, we sought to determine the mechanism by which NE enters tumor cells. Our results show that NE enters into early endosomal antigen-1(+) endosomes in a dynamin- and clathrin-dependent but flotillin-1- and caveolin-1-independent fashion. Cathepsin G (but not proteinase-3) also enters tumor endosomes via the same mechanism. We utilized (125)I-labeled NE to demonstrate that NE binds to the surface of cancer cells. Incubation of radiolabeled NE with lung cancer cells displays a dissociation constant (K(d)) of 284 nm. Because NE is known to bind to heparan sulfate- and chondroitin sulfate-containing proteoglycans, we treated cells with glycanases to remove these confounding factors, which did not significantly diminish cell surface binding or endosomal entry. Thus, NE and CG bind to the surface of cancer cells, presumably to a cell surface receptor, and subsequently undergo clathrin pit-mediated endocytosis.
Alyssa D Gregory; Pamela Hale; David H Perlmutter; A McGarry Houghton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2012-12-31     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35341-50     Citation Subset:  IM    
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
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MeSH Terms
CHO Cells
Cathepsin G / genetics,  metabolism*
Caveolin 1 / genetics,  metabolism
Chondroitin Sulfates / genetics,  metabolism
Clathrin / genetics,  metabolism*
Coated Pits, Cell-Membrane / genetics,  metabolism*
Leukocyte Elastase / genetics,  metabolism*
Lung Neoplasms / genetics,  metabolism*
Neoplasm Proteins / genetics,  metabolism*
Protein Binding / genetics
Protein Transport / genetics
Grant Support
Reg. No./Substance:
0/Caveolin 1; 0/Clathrin; 0/Neoplasm Proteins; 9007-28-7/Chondroitin Sulfates; EC protein, human; EC G; EC Elastase

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