CD133+ renal progenitor cells contribute to tumor angiogenesis

Am J Pathol. 2006 Dec;169(6):2223-35. doi: 10.2353/ajpath.2006.060498.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, CD / metabolism*
  • Carcinoma / blood supply*
  • Cell Differentiation
  • Endothelial Cells / physiology
  • Female
  • Glycoproteins / metabolism*
  • Humans
  • Kidney / cytology*
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / etiology*
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / etiology*
  • Peptides / metabolism*
  • Stem Cells / metabolism*
  • Stem Cells / physiology
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse