Identification of a tumor‐initiating stem cell population in human renal carcinomas

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Abstract
The purpose of the present study was to search for the presence of a tumor‐initiating stem cell population in renal carcinomas. Based on the recent identification of mesenchymal stem cells in normal kidneys, we sorted cells expressing the mesenchymal stem cell marker CD105 from 5 human renal carcinomas. Because the CD105 + but not the CD105 − population showed enhanced tumorigenicity when injected in severely compromised immunodeficient (SCID) mice, we cloned and characterized CD105 + cells and evaluated their stemness, differentiative ability, and serial tumor generation. Characterization of the phenotype of CD105 + clones revealed several stem cell properties: 1 ) clonogenic ability, 2 ) expression of nestin, Nanog, Oct4 stem cell markers, and lack of differentiative epithelial markers, 3 ) ability to grow in non‐adhesive spheroids, 4 ) in vitro differentiation into epithelial and endothelial cell types, and 5 ) generation in vivo of serially transplantable carcinomas containing an undifferentiated CD105 + tumorigenic and a differentiated CD105 − nontumorigenic population. In addition, some vessels present in carcinomas generated from CD105 + clones were of human origin, suggesting the capability of tumor‐initiating stem cells to in vivo differentiate also in endothelial cells. In conclusion, we demonstrate that CD105 + cells and clones derived from renal carcinomas were enriched in tumor‐initiating cells with stem characteristics.—Bussolati, B., Bruno, S., Grange, C., Ferrando, U., Camussi, G. Identification of a tumor‐initiating stem cell population in human renal carcinomas. FASEB J. 22, 3696–3705 (2008)
Funding Information
  • Associazione Italiana per la Ricerca sul Cancro
  • Ministero dell’Istruzione, dell’Università e della Ricerca

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