CD133+ renal progenitor cells contribute to tumor angiogenesis.
In the present study, we tested the hypothesis that resident progenitor cells may contribute to tumor vascularization and growth. CD133+ cells were isolated from 30 human renal carcinomas and characterized as renal resident progenitor cells on the basis of the expression of renal embryonic and mesenchymal stem cell markers. CD133+ progenitors differentiated into endothelial and epithelial cells as the normal CD133+ counterpart present in renal tissue. In the presence of tumor-derived growth factors, these cells were committed to differentiate into endothelial cells able to form vessels in vivo in SCID mice. Undifferentiated CD133+ progenitors were unable to form tumors when transplanted alone in SCID mice. When co-transplanted with renal carcinoma cells, CD133+ progenitors significantly enhanced tumor development and growth. This effect was not attributable to the tumorigenic nature of CD133+ progenitor cells because the same results were obtained with CD133+ cells from normal kidney. CD133+ progenitors contributed to tumor vascularization as the majority of neoformed vessels present within the transplanted tumors were of human origin and derived from the co-transplanted CD133+ progenitors. In conclusion, these results indicate the presence of a renal progenitor cell population in renal carcinomas that may differentiate in endothelial cells and favor vascularization and tumor growth.
Bruno
Stefania
S
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Università di Torino, Ospedale Maggiore S. Giovanni Battista, Corso Dogliotti 14, 10126, Torino, Italy.
Bussolati
Benedetta
B
Grange
Cristina
C
Collino
Federica
F
Graziano
Manuela Efrem
ME
Ferrando
Ugo
U
Camussi
Giovanni
G
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002277:Carcinoma / Q000098:blood supply*; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology*; D007680:Kidney Neoplasms / Q000098:blood supply / Q000209:etiology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010455:Peptides / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse