(HealthDay News) — Acute kidney injury (AKI) seems to promote the development of papillary renal cell carcinoma (pRCC) from single progenitors, according to a study published in Science Translational Medicine.
Anna Julie Peired, PhD, from the University of Florence in Italy, and colleagues examined the role of AKI, which causes DNA damage and repair processes involving increased cell mitosis and polyploidization, in pRCC.
The researchers found that AKI increased the risk for pRCC development and tumor relapse in humans. In mice, lineage tracing of tubular epithelial cells (TECs) after induction of AKI and long-term follow-up showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. In pathways related to AKI, NOTCH1 overexpression in human pRCC was associated with worse outcome and was specific for type 2 pRCC. Papillary adenomas and type 2 pRCCs developed in mice overexpressing NOTCH1 in TECs; this process was accelerated by AKI. Single renal progenitors were identified as the cell of origin in papillary tumors by lineage tracing in mice. Human renal progenitor transcriptome showed similarities to PT1, the suggested cell of origin of human pRCC in single-cell RNA sequencing. In cultured human renal progenitor cells, NOTCH1 overexpression induced tumor-like three-dimensional growth.
“In summary, the results of this study provide evidence that acute organ injury can drive tumorigenesis and, in particular, that AKI promotes the development of pRCC from single renal progenitors through a classical adenoma-carcinoma sequence,” the authors write.
One author disclosed financial ties to the pharmaceutical industry.
Peired AJ, Antonelli G, Angelotti ML. Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells. Sci Transl Med. 12;536. doi: 10.1126/scitranslmed.aaw6003