A perivascular niche for brain tumor stem cells

Cancer Cell. 2007 Jan;11(1):69-82. doi: 10.1016/j.ccr.2006.11.020.

Abstract

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / metabolism
  • Cell Communication / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells* / metabolism
  • Female
  • Gene Expression
  • Glycoproteins / metabolism
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells* / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Peptides / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Peptides