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Article Dans Une Revue Oncotarget Année : 2016

Isolation and characterization of renal cancer stem cells from patient-derived xenografts

Stefania Bruno
  • Fonction : Auteur
Sandy Azzi
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  • PersonId : 942065
Cindy Gallerne
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  • PersonId : 857385
Julien Giron Michel
  • Fonction : Auteur
Giulia Chiabotto
  • Fonction : Auteur
Vincent Lecoz
  • Fonction : Auteur
Cristina Romei
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Grazia Maria Spaggiari
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Annalisa Pezzolo
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Vito Pistoia
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Sophie Gad
Claudine Kieda
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  • PersonId : 870495
Federica Sabatini
  • Fonction : Auteur
Pierre Eid
  • Fonction : Auteur
Bruno Bruno
  • Fonction : Auteur

Résumé

As rapidly developing patient-derived xenografts (PDX) could represent potential sources of cancer stem cells (CSC), we selected and characterized non-cultured PDX cell suspensions from four different renal carcinomas (RCC). Only the cell suspensions from the serial xenografts (PDX-1 and PDX-2) of an undifferentiated RCC (RCC-41) adapted to the selective CSC medium. The cell suspension derived from the original tumor specimen (RCC-41-P-0) did not adapt to the selective medium and strongly expressed CSC-like markers (CD133 and CD105) together with the non-CSC tumor marker E-cadherin. In comparison, PDX-1 and PDX-2 cells exhibited evolution in their phenotype since PDX-1 cells were CD133high/CD105-/Ecadlow and PDX-2 cells were CD133low/CD105-/Ecad-. Both PDX subsets expressed additional stem cell markers (CD146/CD29/OCT4/NANOG/Nestin) but still contained non-CSC tumor cells. Therefore, using different cell sorting strategies, we characterized 3 different putative CSC subsets (RCC-41-PDX-1/CD132+, RCC-41-PDX-2/CD133-/EpCAMlow and RCC-41-PDX-2/CD133+/EpCAMbright). In addition, transcriptomic analysis showed that RCC-41-PDX-2/CD133− over-expressed the pluripotency gene ERBB4, while RCC-41-PDX-2/CD133+ over-expressed several tumor suppressor genes. These three CSC subsets displayed ALDH activity, formed serial spheroids and developed serial tumors in SCID mice, although RCC-41-PDX-1/CD132+ and RCC-41-PDX-2/CD133+ displayed less efficiently the above CSC properties. RCC-41-PDX-1/CD132+ tumors showed vessels of human origin with CSC displaying peri-vascular distribution. By contrast, RCC-41-PDX-2 originated tumors exhibiting only vessels of mouse origin without CSC peri-vascular distribution.Altogether, our results indicate that PDX murine microenvironment promotes a continuous redesign of CSC phenotype, unmasking CSC subsets potentially present in a single RCC or generating ex novo different CSC-like subsets.

Dates et versions

hal-02069078 , version 1 (15-03-2019)

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Meriem Hasmim, Stefania Bruno, Sandy Azzi, Cindy Gallerne, Julien Giron Michel, et al.. Isolation and characterization of renal cancer stem cells from patient-derived xenografts. Oncotarget, 2016, 7 (13), ⟨10.18632/oncotarget.6266⟩. ⟨hal-02069078⟩
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