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Citations to this article

Loss of SPARC in bladder cancer enhances carcinogenesis and progression
Neveen Said, … , Rolf A. Brekken, Dan Theodorescu
Neveen Said, … , Rolf A. Brekken, Dan Theodorescu
Published January 16, 2013
Citation Information: J Clin Invest. 2013;123(2):751-766. https://doi.org/10.1172/JCI64782.
View: Text | PDF | Corrigendum
Research Article Oncology Article has an altmetric score of 12

Loss of SPARC in bladder cancer enhances carcinogenesis and progression

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Abstract

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

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2009 Total
Citations: 2 5 3 3 10 7 7 3 4 4 3 9 2 1 63
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Citations to this article (63)

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Kazakova E, Rakina M, Sudarskikh T, Iamshchikov P, Tarasova A, Tashireva L, Afanasiev S, Dobrodeev A, Zhuikova L, Cherdyntseva N, Kzhyshkowska J, Larionova I
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SK Srivastava, A Ahmad, O Miree, GK Patel, S Singh, RP Rocconi, AP Singh
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Epigenetic basis of cancer health disparities: Looking beyond genetic differences
A Ahmad, S Azim, H Zubair, MA Khan, S Singh, JE Carter, RP Rocconi, AP Singh
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S Sharma, F Xing, Y Liu, K Wu, N Said, R Pochampally, Y Shiozawa, HK Lin, KC Balaji, K Watabe
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A Slusser-Nore, JL Larson-Casey, R Zhang, XD Zhou, S Somji, SH Garrett, DA Sens, JR Dunlevy, RA Winn
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SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations
F Mateo, Ó Meca-Cortés, T Celià-Terrassa, Y Fernández, I Abasolo, L Sánchez-Cid, R Bermudo, A Sagasta, L Rodríguez-Carunchio, M Pons, V Cánovas, M Marín-Aguilera, L Mengual, A Alcaraz, S Schwartz, B Mellado, KY Aguilera, R Brekken, PL Fernández, R Paciucci, TM Thomson
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Oncotarget 2014
Modelling bladder cancer in mice: opportunities and challenges
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W Liu, CJ Vivian, AE Brinker, KR Hampton, E Lianidou, DR Welch
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