Document Detail


Heat shock cognate 70 protein secretion as a new growth arrest signal for cancer cells.
MedLine Citation:
PMID:  19802014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Earlier studies indicated that density-arrested cancer cells released an unidentified growth inhibitor whose secretion was prevented by overexpression of the lysosomal protease cathepsin D (cath D). In this study, this growth inhibitor was purified by affinity chromatography and identified as the heat shock cognate 70 protein (hsc70) based on its peptide microsequencing and specific antibody recognition. Among intracellular proteins, including other heat shock proteins, only constitutive hsc70 was secreted in response to the high-cell density. Moreover, hsc70 secretion from cancer cells was generated by serum deprivation, whereas its cellular concentration did not change. Prevention of Hsc70 secretion by cath D overexpression was associated with the formation of multilayer cell cultures, thus indicating a loss of contact inhibition. In addition, we showed that supplementing the culture medium with purified hsc70 inhibited cell proliferation in the nanomolar range. Conversely, removal of this extracellular hsc70 from the medium by either retention on ADP-agarose or competition at the Hsc70 binding site restored cell proliferation. Hsc70 appears active in human breast cancer cells and hypersecreted by direct cath D inhibition. These results suggest a new role of this secreted hsc70 chaperone in cell proliferation that might account for the higher tumor growth of cancer cells overexpressing cath D.
Authors:
P Nirdé; D Derocq; M Maynadier; M Chambon; I Basile; M Gary-Bobo; M Garcia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-05
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-07     Completed Date:  2010-02-01     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-27     Citation Subset:  IM    
Affiliation:
IRCM, institut de Recherche en Cancérologie de Montpellier, Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Breast Neoplasms / metabolism,  pathology,  physiopathology
Cathepsin D / genetics,  metabolism*
Cell Count
Cell Line
Cell Line, Tumor
Cell Proliferation*
Chromatography, High Pressure Liquid
Culture Media, Serum-Free / pharmacology
Electrophoresis, Polyacrylamide Gel
Female
HSC70 Heat-Shock Proteins / genetics,  metabolism*,  secretion
Humans
Microscopy, Electron, Scanning
Neoplasms / metabolism,  pathology,  physiopathology
RNA Interference
Recombinant Proteins / pharmacology
Signal Transduction / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/HSC70 Heat-Shock Proteins; 0/Recombinant Proteins; EC 3.4.23.5/Cathepsin D
Comments/Corrections

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