Renal cell carcinoma, a metabolic disease

Dr. David Meierhofer, Prof. Dr. Alexander Meissner

October 08, 2020

How do chromophobe renal cell carcinoma (chRCC) cells get nutrients despite poorly developed blood vessels within the tumor? To address this question, we used fluorescent-labeled bovine serum albumin (BSA) to track the uptake of a macro-molecule, a process called macropinocytosis. Compared to healthy kidney cells, chRCC cells showed significant enrichment of macropinocytosis, indicating that this kidney cancer can adapt to nutrient poor conditions. This image features chRCC cells, in blue: nuclei, in red: fluorescent-labeled BSA within chRCC cells.

Metabolic reprogramming is an important hallmark of cancer, which allows cancer cells to adapt to harsh tumor microenvironments (e.g. hypoxia, nutrient-poor conditions). Our research aims to decipher molecular mechanisms in renal cell carcinomas (RCC) with omics approaches. In recent years, our lab discovered many metabolic alterations and mitochondrial malfunctions in renal oncocytoma (Kurschner et al., Oncotarget 2017), papillary RCC (Ahmad et al, Cancers 2019), and chromophobe RCC (Xiao et al., Cancer Research 2020). We are especially interested in how RCC cells recruit nutrients, as we recently identified macropinocytosis as the driver to gain nutrition in chromophobe RCC.

We will shed light on the global cytidine methylation patterns in RCC tissues and cells, use FACS sorting to isolate cancer stem cells and grow organoids of such sub-populations to validate the cancer stem cell characters. Proteome and metabolome profiling of those will identify important regulated metabolic pathways in these cancer stem cells derived from RCC. Evaluation of key findings will be performed by the measurement of protein dynamics (e.g. pulsed stable isotope labeling of amino acids in cell culture (pSILAC)) and the analysis of metabolic fluxes (by isotope tracing) of selected dysregulated pathways.

For a general description of our research please have a look at the website of the Mass Spectrometry group.

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