CD133-expressing stem cells associated with ovarian metastases establish an endothelial hierarchy and contribute to tumor vasculature

Stem Cells. 2009 Mar;27(3):498-508. doi: 10.1634/stemcells.2008-0868.

Abstract

Recruitment and localization of endothelial precursors within tumors is a potential area for the development of therapeutics, because their functional contribution to tumor vasculature is realized to be important for cancer cell survival. However, the exact nature of the recruited cell type and cellular events orchestrating the entire phenomenon remains obscure. We report that human ovarian cancer is frequently associated with cells expressing the stem cell surface marker CD133. We further show that these CD133-expressing cells are nontumorigenic in nature, and they augment tumor development through their vasculogenic potential. This cell population is attracted by cancer stem cells (CSCs) and retains a direct physical association within the CSC-derived spheroids. Our study further delineates the contribution of these vasculogenic CD133(+) stem cells, termed by us as endothelial stem cells (EnSCs) to the developing tumor vasculature during disease progression. In support of their being stem cells, the EnSCs have a capability of establishing an entire endothelial cell hierarchy. We conclude that such EnSCs play a crucial role in ensuring the development of long-term tumor vasculature to complement CSC-driven tumor development and disease progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Female
  • Flow Cytometry
  • Glycoproteins / metabolism*
  • Humans
  • Middle Aged
  • Models, Biological
  • Neoplasm Metastasis / physiopathology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / physiology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Peptides / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / physiology*

Substances

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