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ROCK1 Inhibition Promotes the Self-Renewal of a Novel Mouse Mammary Cancer Stem Cell†‡§

  1. David J. Castro1,
  2. Jochen Maurer1,
  3. Lionel Hebbard2,
  4. Robert G. Oshima1,¶,*

Article first published online: 19 DEC 2012

DOI: 10.1002/stem.1224

Issue

STEM CELLS

STEM CELLS

Volume 31, Issue 1, pages 12–22, January 2013

Additional Information

How to Cite

Castro, D. J., Maurer, J., Hebbard, L. and Oshima, R. G. (2013), ROCK1 Inhibition Promotes the Self-Renewal of a Novel Mouse Mammary Cancer Stem Cell. STEM CELLS, 31: 12–22. doi: 10.1002/stem.1224

Author Information

  1. 1

    Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California, USA

  2. 2

    Storr Liver Unit Cancer Group, Westmead Millennium Institute, Westmead, New South Wales, Australia

  1. Telephone: 858-646-3147; Fax: 858-713-6268;

*10901 N. Torrey Pines Road, La Jolla, California 92037, USA

  1. †

    Author contributions: D.C. and J.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; L.H.: collection and/or assembly of data; R.O.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript. D.J.C. and J.M. contributed equally to this article.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLSEXPRESS September 7, 2012.

  4. Telephone: 858-646-3147; Fax: 858-713-6268;

Publication History

  1. Issue published online: 19 DEC 2012
  2. Article first published online: 19 DEC 2012
  3. Accepted manuscript online: 7 SEP 2012 01:03PM EST
  4. Manuscript Accepted: 10 AUG 2012
  5. Manuscript Received: 5 JUN 2012

Funded by

  • DOD Breast Cancer Research Program. Grant Number: BC093655
  • NCI Cancer Center. Grant Number: 5 P30 CA030199
  • NCI Postdoctoral Training. Grant Number: T32 CA121949

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Keywords:

  • Breast cancer;
  • Cancer stem cell;
  • Epithelial-mesenchymal transition;
  • Keratin;
  • ROCK1

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. Stem Cells2013;31:12–22

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