| Heat shock cognate 70 protein secretion as a new growth arrest signal for cancer cells. | |
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MedLine Citation:
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PMID: 19802014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P Nirdé; D Derocq; M Maynadier; M Chambon; I Basile; M Gary-Bobo; M Garcia |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-05 |
Journal Detail:
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Title: Oncogene Volume: 29 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-07 Completed Date: 2010-02-01 Revised Date: 2010-09-28 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 117-27 Citation Subset: IM |
Affiliation:
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IRCM, institut de Recherche en Cancérologie de Montpellier, Montpellier, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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