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

Autor: Stefania Bruno, Cristina Grange, Giovanni Camussi, Ugo Ferrando, Benedetta Bussolati
Rok vydání: 2008
Předmět:
Zdroj: The FASEB Journal. 22:3696-3705
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.08-102590
Popis: 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 carcino- mas. Because the CD105 but not the CD105 popu- lation 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 pheno- type of CD105 clones revealed several stem cell properties: 1) clonogenic ability, 2) expression of nes- tin, Nanog, Oct4 stem cell markers, and lack of differ- entiative 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 differ- entiated CD105 nontumorigenic population. In addi- tion, 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-initiat- ing 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, 000-000 (2008)
Databáze: OpenAIRE