Document Detail


Loss of SPARC in bladder cancer enhances carcinogenesis and progression.
MedLine Citation:
PMID:  23321672     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Secreted protein acidic and rich in cysteine (SPARC) has been implicated in multiple aspects of human cancer. However, its role in bladder carcinogenesis and metastasis are unclear,with some studies suggesting it may be a promoter and others arguing the opposite. Using a chemical carcinogenesis model in Sparc-deficient mice and their wild-type littermates, we found that loss of SPARC accelerated the development of urothelial preneoplasia (atypia and dysplasia), neoplasia, and metastasis and was associated with decreased survival. SPARC reduced carcinogen-induced inflammation and accumulation of reactive oxygen species as well as urothelial cell proliferation. Loss of SPARC was associated with an inflammatory phenotype of tumor-associated macrophages and fibroblasts, with concomitant increased activation of urothelial and stromal NF-κB and AP1 in vivo and in vitro. Syngeneic spontaneous and experimental metastasis models revealed that tumor- and stroma-derived SPARC reduced tumor growth and metastasis through inhibition of cancer-associated inflammation and lung colonization. In human bladder tumor tissues, the frequency and intensity of SPARC expression were inversely correlated with disease-specific survival. These results indicate that SPARC is produced by benign and malignant compartments of bladder carcinomas where it functions to suppress bladder carcinogenesis, progression, and metastasis.
Authors:
Neveen Said; Henry F Frierson; Marta Sanchez-Carbayo; Rolf A Brekken; Dan Theodorescu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-66     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cell Cycle Proteins / genetics,  metabolism
Cell Line, Tumor
Disease Models, Animal
Disease Progression
Female
Glycoproteins / deficiency*,  genetics,  metabolism
Humans
Inflammation Mediators / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Nitrosamines / toxicity
Osteonectin
Precancerous Conditions / etiology,  genetics,  metabolism
RNA, Small Interfering / genetics
Tumor Suppressor Proteins / deficiency*,  genetics,  metabolism
Urinary Bladder Neoplasms / etiology*,  genetics,  metabolism,  secondary
Urothelium / metabolism,  pathology
Grant Support
ID/Acronym/Agency:
CA118240/CA/NCI NIH HHS; CA143971/CA/NCI NIH HHS; P30 CA044579/CA/NCI NIH HHS; R01 CA143971/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Glycoproteins; 0/Inflammation Mediators; 0/Nitrosamines; 0/Osteonectin; 0/RNA, Small Interfering; 0/SPARC protein, human; 0/SPARC protein, mouse; 0/Tumor Suppressor Proteins; 924-16-3/dibutylnitrosamine
Comments/Corrections
Erratum In:
J Clin Invest. 2013 Sep 3;123(9):4089

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


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