ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell

Stem Cells. 2013 Jan;31(1):12-22. doi: 10.1002/stem.1224.

Abstract

The differentiation of stem-like tumor cells may contribute to the cellular heterogeneity of breast cancers. We report the propagation of highly enriched mouse mammary cancer stem cells that retain the potential to differentiate both in vivo and in culture and their use to identify chemical compounds that influence both self-renewal and differentiation. We identify epithelial tumor-initiating cells (ETICs) that express lineage markers of both basal and luminal mammary cell lineages and retain the potential, from even single cells, to generate heterogeneous tumors similar to the tumor of origin. ETICs can progress through a Rho-associated coiled-coil containing protein kinase 1 dependent, epithelial to mesenchymal transition to generate mesenchymal tumor-initiating cells capable of initiating tumors of limited heterogeneity. The propagation of ETICs may allow for the identification of new therapeutic compounds that may inhibit or prevent progression of some types of breast cancer.

Publication types

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

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Profiling
  • Mammary Glands, Animal / pathology
  • Mammary Neoplasms, Animal / metabolism*
  • Mammary Tumor Virus, Mouse / genetics
  • Mice
  • Mice, Transgenic
  • Neoplastic Stem Cells / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Tumor Cells, Cultured
  • Wnt1 Protein / metabolism
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • RNA, Small Interfering
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Rock1 protein, mouse
  • Rock2 protein, mouse
  • rho-Associated Kinases