Leptin Promotes Invasiveness of Murine Renal Cancer Cells Via Extracellular Signal-Regulated Kinases and Rho Dependent Pathway

No AccessJournal of UrologyInvestigative urology1 Oct 2006Leptin Promotes Invasiveness of Murine Renal Cancer Cells Via Extracellular Signal-Regulated Kinases and Rho Dependent Pathwayis companion ofSignificance of Macroscopic Tumor Necrosis as a Prognostic Indicator for Renal Cell Carcinoma Akio Horiguchi, Makoto Sumitomo, Junichi Asakuma, Takako Asano, Rong Zheng, Tomohiko Asano, David M. Nanus, and Masamichi Hayakawa Akio HoriguchiAkio Horiguchi Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author , Makoto SumitomoMakoto Sumitomo Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author , Junichi AsakumaJunichi Asakuma Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author , Takako AsanoTakako Asano Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author , Rong ZhengRong Zheng Urological Oncology Research Laboratory, Department of Urology, Division of Hematology and Medical Oncology, and Department of Medicine, Weill Medical College of Cornell University, New York, New York More articles by this author , Tomohiko AsanoTomohiko Asano Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author , David M. NanusDavid M. Nanus Urological Oncology Research Laboratory, Department of Urology, Division of Hematology and Medical Oncology, and Department of Medicine, Weill Medical College of Cornell University, New York, New York Financial interest and/or other relationship with Amgen. More articles by this author , and Masamichi HayakawaMasamichi Hayakawa Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2006.06.040AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Obesity is a significant risk factor for renal cell carcinoma. The adipocyte derived cytokine leptin, which controls body weight homeostasis through food intake and energy expenditure, recently provided a potential link between obesity and cancer development. We examined whether leptin promotes the invasiveness of renal cancer cells and we investigated its underlying signaling pathway. Materials and Methods: Leptin receptor expression in the 6 human renal cancer cell lines Caki-1, ACHN, 769P, A498, SKRC44 and SKRC49, and in the murine renal cancer cell line Renca was examined by reverse transcriptase-polymerase chain reaction and Western blotting. The effect of leptin on renal cancer cell invasiveness was assessed by the invasion of cells through Matrigel™ coated Transwell® inserts. Leptin induced intracellular signaling was examined by Western blotting. Results: Leptin receptor was detected in all renal cancer cells examined at the mRNA and protein levels. Leptin increased Renca cell invasiveness at 1 ng/ml (p <0.05). There was up to 3-fold invasiveness compared to untreated cells at 100 ng/ml with the activation of extracellular signal-regulated kinases and rho guanosine triphosphatase (p <0.01). Leptin induced activation of rho guanosine triphosphatase was inhibited not only by the rho kinase inhibitor Y27632, but also by the MEK1 inhibitor PD98059, of which each inhibited leptin induced invasion of Renca cells (p <0.01). Conclusions: Leptin promoted the invasiveness of murine renal cancer cells via extracellular signal-regulated kinases and rho guanosine triphosphatase dependent pathways. Rho guanosine triphosphatase was a downstream effector of extracellular signal-regulated kinases in leptin induced invasion. Leptin signaling could have a key role in renal cell carcinoma invasion. References 1 : Recombinant ob protein reduces feeding and body weight in the ob/ob mouse. J Clin Invest1995; 96: 2065. Google Scholar 2 : Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol2000; 68: 437. Google Scholar 3 : Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest2000; 106: 501. 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Google Scholar © 2006 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology9 Nov 2018Significance of Macroscopic Tumor Necrosis as a Prognostic Indicator for Renal Cell Carcinoma Volume 176Issue 4October 2006Page: 1636-1641 Advertisement Copyright & Permissions© 2006 by American Urological AssociationKeywordskidneyobesitykidney neoplasmsneoplasm invasivenessMetricsAuthor Information Akio Horiguchi Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author Makoto Sumitomo Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author Junichi Asakuma Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author Takako Asano Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author Rong Zheng Urological Oncology Research Laboratory, Department of Urology, Division of Hematology and Medical Oncology, and Department of Medicine, Weill Medical College of Cornell University, New York, New York More articles by this author Tomohiko Asano Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author David M. Nanus Urological Oncology Research Laboratory, Department of Urology, Division of Hematology and Medical Oncology, and Department of Medicine, Weill Medical College of Cornell University, New York, New York Financial interest and/or other relationship with Amgen. More articles by this author Masamichi Hayakawa Department of Urology, National Defense Medical College, Saitama, Japan More articles by this author Expand All Advertisement PDF downloadLoading ...