The developmental programme for genesis of the entire kidney is recapitulated in Wilms tumour

PLoS One. 2017 Oct 17;12(10):e0186333. doi: 10.1371/journal.pone.0186333. eCollection 2017.


Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain. To address the question of the involvement of UB, we assessed 55 Wilms tumours for the molecular features of MM and UB using gene expression profiling, immunohistochemsitry and immunofluorescence. Expression profiling primarily based on the Genitourinary Molecular Anatomy Project data identified molecular signatures of the UB and collecting duct as well as those of the proximal and distal tubules in the triphasic histology group. We performed immunolabeling for fetal kidneys and WTs. We focused on a central epithelial blastema pattern which is the characteristic of triphasic histology characterized by UB-like epithelial structures surrounded by MM and MM-derived epithelial structures, evoking the induction/aggregation phase of the developing kidney. The UB-like epithelial structures and surrounding MM and epithelial structures resembling early glomerular epithelium, proximal and distal tubules showed similar expression patterns to those of the developing kidney. These observations indicate WTs can arise from a precursor cell capable of generating the entire kidney, such as the cells of the intermediate mesoderm from which both the MM and UB are derived. Moreover, this provides an explanation for the variable histological features of mesenchymal to epithelial differentiation seen in WT.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Differentiation / genetics
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Fetus / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Humans
  • Kidney / growth & development
  • Kidney / metabolism*
  • Kidney / pathology
  • Mesoderm / growth & development
  • Mesoderm / metabolism*
  • Organ Culture Techniques
  • Organogenesis / genetics
  • Ureter / growth & development
  • Ureter / metabolism*
  • Wilms Tumor / genetics*
  • Wilms Tumor / pathology

Grant support

We acknowledge funding from Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, 25460427, Prof. Ryuji Fukuzawa, Joint Research Project Grant from the Japan Society for the Promotion of Science, Prof. Ryuji Fukuzawa and from the Ministry of Business, Innovation, and Employment of Zealand, Prof Ian M Morison.