[Frontiers in Bioscience E3, 187-193, January 1, 2011]

Heterogeneity of mitochondrial energy metabolism in classical triphasic Wilms' tumor

Rene G. Feichtinger1, Daniel Neureiter2, Brigitte Royer-Pokora3, Johannes A. Mayr1, Franz A. Zimmermann1, Neil Jones1, Christian Koegler4, Manfred Ratschek4, Wolfgang Sperl1, Barbara Kofler1

1Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020 Salzburg, Austria, 2Department of Pathology, University Hospital Salzburg, Paracelsus Medical University, Muellner Hauptstr. 48, A-5020 Salzburg, Austria, 3Institute of Human Genetics and Anthropology, Heinrich Heine University of Duesseldorf, D40001 Duesseldorf, Germany, 4Institute of Pathology, Medical University of Graz, A-8036 Graz, Austria

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Ethics
3.2. Samples 3.3. Spectrophotometric detection of OXPHOS enzyme and citrate synthase activities 3.4. Western blot analysis
3.5. Immunohistochemical staining
3.6. Determination of mitochondrial DNA copy number
4. Results
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

Metabolic changes are observed in a variety of tumors. The nature of the changes in aerobic energy metabolism differs between tumor types. Therefore, immunohistochemical staining, enzymatic measurements and immunoblot analysis were used to determine alterations of oxidative phosphorylation (OXPHOS) in classic triphasic Wilms' Tumor (WT). Our studies revealed that the epithelial, stromal and blastemal elements of this tumor differ in their energy metabolism. Compared to unaffected kidney tissue, normal mitochondrial mass was observed in the epithelial and blastemal regions of WT, whereas the stroma showed a massive down-regulation of mitochondria, as indicated by low porin content, low citrate synthase activity, and reduced mtDNA copy number. All OXPHOS enzyme activities were reduced in all WT samples, with the exception of two epithelial-dominant cases, which showed up-regulation of complex III activity compared to control kidney tissues. Interestingly, our studies show that, even within a specific tumor entity, cell-type-specific alterations of aerobic energy metabolism can occur, although all cell types showed a clear tendency toward a reduced aerobic energy metabolism.