| Loss of SPARC in bladder cancer enhances carcinogenesis and progression. | |
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MedLine Citation:
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PMID: 23321672 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Neveen Said; Henry F Frierson; Marta Sanchez-Carbayo; Rolf A Brekken; Dan Theodorescu |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-16 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-04-19 Completed Date: 2013-05-13 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 751-66 Citation Subset: AIM; IM |
Affiliation:
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Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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 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:
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CA118240/CA/NCI NIH HHS; CA143971/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Glycoproteins; 0/Inflammation Mediators; 0/Nitrosamines; 0/RNA, Small Interfering; 0/SPARC protein, human; 0/SPARC protein, mouse; 0/Tumor Suppressor Proteins; 924-16-3/dibutylnitrosamine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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