Invasive prostate cancer cells are tumor initiating cells that have a stem cell-like genomic signature

Clin Exp Metastasis. 2009;26(5):433-46. doi: 10.1007/s10585-009-9242-2. Epub 2009 Feb 17.


Development of metastasis is a leading cause of cancer-induced death. Acquisition of an invasive tumor cell phenotype suggests loss of cell adhesion and basement membrane breakdown during a process termed epithelial-to-mesenchymal transition (EMT). Recently, cancer stem cells (CSC) were discovered to mediate solid tumor initiation and progression. Prostate CSCs are a subpopulation of CD44(+) cells within the tumor that give rise to differentiated tumor cells and also self-renew. Using both primary and established prostate cancer cell lines, we tested the assumption that CSCs are more invasive. The ability of unsorted cells and CD44-positive and -negative subpopulations to undergo Matrigel invasion and EMT was evaluated, and the gene expression profiles of these cells were analyzed by microarray and a subset confirmed using QRT-PCR. Our data reveal that a subpopulation of CD44(+) CSC-like cells invade Matrigel through an EMT, while in contrast, CD44(-) cells are non-invasive. Furthermore, the genomic profile of the invasive cells closely resembles that of CD44(+)CD24(-) prostate CSCs and shows evidence for increased Hedgehog signaling. Finally, invasive cells from DU145 and primary prostate cancer cells are more tumorigenic in NOD/SCID mice compared with non-invasive cells. Our data strongly suggest that basement membrane invasion, an early and necessary step in metastasis development, is mediated by these potential cancer stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD24 Antigen / biosynthesis
  • Epithelium / pathology
  • Genomics
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Male
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Stem Cells / metabolism


  • CD24 Antigen
  • Hyaluronan Receptors