Wnt-responsive cancer stem cells are located close to distorted blood vessels and not in hypoxic regions in a p53-null mouse model of human breast cancer

Tegy J. Vadakkan, John D. Landua, Wen Bu, Wei Wei, Fuhai Li, Stephen T. Wong, Mary E. Dickinson, Jeffrey M. Rosen, Michael T. Lewis, Mei Zhang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Cancer stem cells (CSCs, or tumor-initiating cells) may be responsible for tumor formation in many types of cancer, including breast cancer. Using high-resolution imaging techniques, we analyzed the relationship between a Wnt-responsive, CSC-enriched population and the tumor vasculature using p53-null mouse mammary tumors transduced with a lentiviral Wnt signaling reporter. Consistent with their localization in the normal mammary gland, Wnt-responsive cells in tumors were enriched in the basal/myoepithelial population and generally located in close proximity to blood vessels. The Wnt-responsive CSCs did not colocalize with the hypoxia-inducible factor 1α-positive cells in these p53-null basal-like tumors. Average vessel diameter and vessel tortuosity were increased in p53-null mouse tumors, as well as in a human tumor xenograft as compared with the normal mammary gland. The combined strategy of monitoring the fluorescently labeled CSCs and vasculature using high-resolution imaging techniques provides a unique opportunity to study the CSC and its surrounding vasculature.

Original languageEnglish (US)
Pages (from-to)857-866
Number of pages10
JournalStem Cells Translational Medicine
Volume3
Issue number7
DOIs
StatePublished - 2014

Keywords

  • Cancer stem cells
  • In vivo optical imaging
  • Microvasculature
  • P53
  • Signal transduction
  • Stem cell microenvironment

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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