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Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells
- Source :
- Università degli studi di Firenze-IRIS, Peired, A J, Antonelli, G, Angelotti, M L, Allinovi, M, Guzzi, F, Sisti, A, Semeraro, R, Conte, C, Mazzinghi, B, Nardi, S, Melica, M E, De Chiara, L, Lazzeri, E, Lasagni, L, Lottini, T, Landini, S, Giglio, S, Mari, A, Di Maida, F, Antonelli, A, Porpiglia, F, Schiavina, R, Ficarra, V, Facchiano, D, Gacci, M, Serni, S, Carini, M, Netto, G J, Roperto, R M, Magi, A, Christiansen, C F, Rotondi, M, Liapis, H, Anders, H-J, Minervini, A, Raspollini, M R & Romagnani, P 2020, ' Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells ', Science Translational Medicine, vol. 12, no. 536, eaaw6003 . https://doi.org/10.1126/scitranslmed.aaw6003, Science Translational Medicine
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Abstract
- Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.
- Subjects :
- Adenoma
0301 basic medicine
papillary renal cell carcinoma
medicine.disease_cause
urologic and male genital diseases
DISEASE
PATHWAY
PROTECTS
Mice
03 medical and health sciences
0302 clinical medicine
AKI
NOTCH1
REGENERATION
Renal cell carcinoma
Biomarkers, Tumor
ABLATION
medicine
Carcinoma
Animals
Progenitor cell
RECURRENCE
Carcinoma, Renal Cell
RECEPTOR
Papillary renal cell carcinomas
business.industry
Stem Cells
Papillary Adenoma
Acute kidney injury
renal carcinoma
General Medicine
Acute Kidney Injury
medicine.disease
TUMORS
Kidney Neoplasms
3. Good health
NOTCH
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
GROWTH
Neoplasm Recurrence, Local
Stem cell
Carcinogenesis
business
Subjects
Details
- Language :
- English
- ISSN :
- 19466242 and 19466234
- Volume :
- 12
- Issue :
- 536
- Database :
- OpenAIRE
- Journal :
- Science Translational Medicine
- Accession number :
- edsair.doi.dedup.....c7a5cb77c0bad35edb909f253e0a96e8
- Full Text :
- https://doi.org/10.1126/scitranslmed.aaw6003