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

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) an 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.