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 nonadhesive 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
Benedetta
B
Department of Internal Medicine, Center for Molecular Biotechnology, Turin, Italy.
Bruno
Stefania
S
Grange
Cristina
C
Ferrando
Ugo
U
Camussi
Giovanni
G
D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis; D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation; D002469:Cell Separation; D002999:Clone Cells; D000071063:Endoglin; D042783:Endothelial Cells / Q000473:pathology; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000473:pathology*; D000071317:Nanog Homeobox Protein; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D064231:Nestin; D050814:Octamer Transcription Factor-3 / Q000032:analysis / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000096:biosynthesis
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; C486780:NANOG protein, human; C577484:NES protein, human; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011956:Receptors, Cell Surface