Abstract
Abstract The proximal tubular segments of the kidney are extremely energy demanding, rendering this epithelium exceptionally sensitive to ischemic insults. Acute renal injury is a potentially life threatening condition, where the tubular cells detach and die. However, the tubules of injured kidneys have a substantial regenerative ability, and epithelial continuity, can with proper supportive care be restored. The cellular source of regeneration has been debated and until now the proximal tubules has been considered a completely homogenous cellular epithelium. Using an assay based on aldehyde dehydrogenase (ALDH) activity followed by FACS, we have recently discovered a cell with progenitor cell characteristics scattered within the proximal tubules of the kidney. These novel proximal tubule rare cells (PTRCs) expressed stem cell markers CD133 and CD24, as well as intermediate filaments not normally seen in PTs. The gene expression profile of these cells shows a striking resemblance to that of papillary renal cell carcinoma (pRCC) and the gene signatures are also associated with a worse prognosis in clear cell renal carcinoma. Additionally, cells positive for PTRC-markers were seen in regenerating tubules after acute kidney injury. We have characterized these cells further at an ultra structural level, using electron microscopy. The cells were small, flask shaped and had a more densely packed chromatin pattern and drastically fewer mitochondria than the surrounding proximal tubular cells, indicating a different metabolic state. We suggest that these cells, in contrast to the surrounding highly oxygen dependent proximal tubular cells, constitute renal reserve cell pool capable of surviving ischemic renal injury with a capacity to spearhead subsequent tubular repopulation. We suggest that the increased probability for survival of these cells is due to their low mitochondrial content, structural robustness and anti-apoptotic signaling. Also, due to the considerable transcriptional similarities between pRCC, renal adenomas and the PTRCs we hypothesize that pRCC may arise through multistep oncogenic transformation of PTRCs. Citation Format: Jennifer Hansson, Kjell Hultenby, Catharina Cramnert, David Lindgren, Håkan Axelson, Martin E. Johansson. Characterization of a novel cell type in human renal proximal tubules with connection to renal cell carcinoma development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5010. doi:10.1158/1538-7445.AM2013-5010
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