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(American Journal of Pathology. 2006;169:2223-2235.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060498

CD133⁺ Renal Progenitor Cells Contribute to Tumor Angiogenesis

Stefania Bruno^*, Benedetta Bussolati^*, Cristina Grange^*, Federica Collino^*, Manuela Efrem Graziano, Ugo Ferrando and Giovanni Camussi^*

From the Dipartimento di Medicina Interna and Centro Ricerca Medicina Sperimentale,^* Cattedra di Nefrologia, Università di Torino, Torino; and the Divisione di Urologia, Ospedale San Giovanni Battista, Torino, Italy

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.

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