Heterogeneity of mitochondrial energy metabolism in classical triphasic Wilms' tumor

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, celltype- specific alterations of aerobic energy metabolism can occur, although all cell types showed a clear tendency toward a reduced aerobic energy metabolism.