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Evidence of renal angiomyolipoma neoplastic stem cells arising from renal epithelial cells

Author

Listed:
  • Ana Filipa Gonçalves

    (University of Zurich
    University Hospital Zurich)

  • Mojca Adlesic

    (University of Zurich
    Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center - University of Freiburg)

  • Simone Brandt

    (University Hospital Zurich)

  • Tomas Hejhal

    (University of Zurich)

  • Sabine Harlander

    (University of Zurich)

  • Lukas Sommer

    (University of Zurich)

  • Olga Shakhova

    (University of Zurich
    University Hospital Zurich)

  • Peter J. Wild

    (University Hospital Zurich)

  • Ian J. Frew

    (University of Zurich
    Oncology and Stem Cell Transplantation, Faculty of Medicine, Medical Center - University of Freiburg
    University of Zurich
    University of Freiburg)

Abstract

Renal angiomyolipomas (AML) contain an admixture of clonal tumour cells with features of several different mesenchymal lineages, implying the existence of an unidentified AML neoplastic stem cell. Biallelic inactivation of TSC2 or TSC1 is believed to represent the driving event in these tumours. Here we show that TSC2 knockdown transforms senescence-resistant cultured mouse and human renal epithelial cells into neoplastic stem cells that serially propagate renal AML-like tumours in mice. mTOR inhibitory therapy of mouse AML allografts mimics the clinical responses of human renal AMLs. Deletion of Tsc1 in mouse renal epithelia causes differentiation in vivo into cells expressing characteristic AML markers. Human renal AML and a renal AML cell line express proximal tubule markers. We describe the first mouse models of renal AML and provide evidence that these mesenchymal tumours originate from renal proximal tubule epithelial cells, uncovering an unexpected pathological differentiation plasticity of the proximal tubule.

Suggested Citation

  • Ana Filipa Gonçalves & Mojca Adlesic & Simone Brandt & Tomas Hejhal & Sabine Harlander & Lukas Sommer & Olga Shakhova & Peter J. Wild & Ian J. Frew, 2017. "Evidence of renal angiomyolipoma neoplastic stem cells arising from renal epithelial cells," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01514-3
    DOI: 10.1038/s41467-017-01514-3
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