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The Association of CXCR3 and Renal Cell Carcinoma Metastasis

2014; Lippincott Williams & Wilkins; Volume: 192; Issue: 2 Linguagem: Inglês

10.1016/j.juro.2014.01.100

1527-3792

Takanobu Utsumi, Takahito Suyama, Yusuke Imamura, Miki Fuse, Shinichi Sakamoto, Naoki Nihei, Takeshi Ueda, Hiroyoshi Suzuki, Naohiko Seki, Tomohiko Ichikawa,

Cancer Immunotherapy and Biomarkers

No AccessJournal of UrologyInvestigative Urology1 Aug 2014The Association of CXCR3 and Renal Cell Carcinoma Metastasis Takanobu Utsumi, Takahito Suyama, Yusuke Imamura, Miki Fuse, Shinichi Sakamoto, Naoki Nihei, Takeshi Ueda, Hiroyoshi Suzuki, Naohiko Seki, and Tomohiko Ichikawa Takanobu UtsumiTakanobu Utsumi Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan Department of Urology, Toho University Sakura Medical Center, Japan , Takahito SuyamaTakahito Suyama Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan , Yusuke ImamuraYusuke Imamura Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada , Miki FuseMiki Fuse Department of Urology and Neurology, Continence Center, Dokkyo Medical University, Tochigi, Japan , Shinichi SakamotoShinichi Sakamoto Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan , Naoki NiheiNaoki Nihei Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan , Takeshi UedaTakeshi Ueda Prostate Center and Division of Urology, Chiba Cancer Center, Japan , Hiroyoshi SuzukiHiroyoshi Suzuki Department of Urology, Toho University Sakura Medical Center, Japan , Naohiko SekiNaohiko Seki Department of Urology, Toho University Sakura Medical Center, Japan , and Tomohiko IchikawaTomohiko Ichikawa Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan View All Author Informationhttps://doi.org/10.1016/j.juro.2014.01.100AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Renal cell carcinoma expresses CXCR3 but the function of CXCR3 in renal cell carcinoma has not been clarified. We explored the function of CXCR3 in renal cell carcinoma and investigated CXCR3 regulating factors. Materials and Methods: We obtained 56 clinical samples of clear cell renal cell carcinoma and corresponding normal renal tissue samples from the surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As renal cell carcinoma cell lines, we used 786-O, ACHN and Caki-1. The expression profiles of CXCR3 and its splice variants were examined. For functional analyses 786-O and interferon-γ inducible 10 kDa protein or IP-10 (CXCL10) were selected as representatives. Results: CXCR3 and its ligands were abundant in renal cell carcinoma samples compared to corresponding normal kidney samples. The CXCR3-A-to-CXCR3-B ratio was 1.5 times higher in renal cell carcinoma samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion, and these effects were inhibited by neutralizing antibody. Phosphorylated RhoA and pro/active matrix metalloproteinase-9 expression was up-regulated by CXCL10 treatment. In clinical samples CXCR3 and CXCR3-A expression was significantly higher in metastatic than in nonmetastatic carcinoma samples. Finally, the expression of CXCR3-A and HIF-1α correlated significantly in clinical samples. In 786-O treatment with CoCl2 up-regulated CXCR3 and HIF-1α expression 4.5 and 2.2-fold, respectively. Conclusions: We determined the association of CXCR3 and renal cell carcinoma metastasis. CXCR3 expression may be regulated by hypoxia. References 1 : Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev2008; 34: 193. Google Scholar 2 : Metastatic renal cell carcinoma. Curr Treat Options Oncol2003; 4: 385. Google Scholar 3 : Chemokines; progress toward identifying molecular targets for therapeutic agents. Trends Biotechnol1996; 14: 46. Google Scholar 4 : Chemokines and leukocyte traffic. 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Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 192Issue 2August 2014Page: 567-574 Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.KeywordscarcinomaanoxiaCXCR3 proteinrenal cellhumankidneyneoplasm metastasisAcknowledgmentsHisayo Karahi provided technical assistance.MetricsAuthor Information Takanobu Utsumi Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan Department of Urology, Toho University Sakura Medical Center, Japan More articles by this author Takahito Suyama Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan More articles by this author Yusuke Imamura Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada More articles by this author Miki Fuse Department of Urology and Neurology, Continence Center, Dokkyo Medical University, Tochigi, Japan More articles by this author Shinichi Sakamoto Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan More articles by this author Naoki Nihei Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan More articles by this author Takeshi Ueda Prostate Center and Division of Urology, Chiba Cancer Center, Japan More articles by this author Hiroyoshi Suzuki Department of Urology, Toho University Sakura Medical Center, Japan More articles by this author Naohiko Seki Department of Urology, Toho University Sakura Medical Center, Japan More articles by this author Tomohiko Ichikawa Department of Functional Genomics, Chiba University Graduate School of Medicine, Japan More articles by this author Expand All Advertisement PDF downloadLoading ...