High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment
- 149 Downloads
End-stage renal disease (ESRD) and acquired cystic renal disease (ACRD) are associated with high risk of development of renal cell tumors (RCT) displaying unusual phenotype and genotype. The underlying molecular mechanism is not yet known. To explore the molecular microenvironment, we have established the expression profile of ESRD/ACRD kidneys. RNA extracted from normal and ESRD/ACRD kidneys and distinct types of RCT was subjected to Affymetrix HG U133 micro array analysis. A gene expression signature indicated cancer-related biological processes in the remodeling of ESRD/ACRD kidneys. Quantitative RT-PCR studies confirmed a specific gene signature including a functional group of inflammatory cytokines and also cytokeratins associated with stem cell characteristics of epithelial cells. Several of the signature genes including the SCEL were expressed in ESRD/ACRD-associated papillary RCT as well. Immunohistological analysis confirmed the expression of CXCL8 and its receptor CXCR2 as well as the expression of SCEL in hyperplastic tubular, cystic, and papillary structures and RCTs in ESRD/ACRD kidney. Our data indicates that ESRD/ACRD is a novel disease and the inflammatory microenvironment altered plasticity, and stem cell characteristics of epithelial cells may be associated with the high risk of tumor development.
KeywordsEnd-stage kidney disease Gene expression signature Inflammatory microenvironment Tumor development CXCL8 CXCR2 SCEL
This work was supported by a grant of the Else-Kröner-Fresenius Stiftung, Homburg, Germany and in part by the Medical Faculty, University of Pécs, Hungary (PTE AOK KA2014/1). The authors express their appreciation to Drs. G. Staehler, B. Schulze-Brüggemann, D. Ferluga, and Mr. D. Cranston for making end-stage kidneys available and to B. Veszpremi for collecting fetal kidneys. The sciellin antibody (SC4) was kindly provided by Dr. H.P. Baden (Massachusetts General Hospital, Boston, USA).
AN and GK designed the study and wrote the manuscript. AN and DZ evaluated the array expression study. AN and EW carried out the RT-PCR analysis. AN and GK performed the immunohistochemistry.
Compliance with ethical standards
Conflicts of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 1.U.S. Renal Data System. USRDS 2013. Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; 2013.Google Scholar
- 10.Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, et al. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol. 2006;30:141–53.CrossRefPubMedGoogle Scholar
- 14.Moskowith DW, Bonar SL, Marcus MD. Epidermal Growth factor (EGF) content of human and mouse (CPK) renal cysts. Am J Kidney Dis. 1989;14:435–6.Google Scholar
- 22.Varney ML, Li A, Dave BJ, Bucana CD, Johansson SL, Singh RK. Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype. Clin Exp Metastasis. 2003;20:723–31.CrossRefPubMedGoogle Scholar
- 26.Virchow R. Die krankhaften Geschwülste (Dreissig Vorlesungen, gehalten wahrend des Wintersemesters 1862–1863) Band I. Berlin, Germany: August Hirschwald.Google Scholar