Epidermal growth factor/heat shock protein 27 pathway regulates vasculogenic mimicry activity of breast cancer stem/progenitor cells

Che Hsin Lee, Yu Ting Wu, Hung Chun Hsieh, Yun Yu, Alice L. Yu, Wen Wei Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

33 Scopus citations

Abstract

Tumor vascularization, which is mainly contributed by angiogenesis and vascularization, is necessary for tumor maintenance and progression. Vasculogenic mimicry (VM), vascular-like channels which are lack of the involvement of endothelial cells, has been observed in aggressive cancers and also involves in tumor vascularization. Breast cancer stem/progenitor cells (BCSCs) have been identified as a subpopulation of breast cancer cells with markers of CD24-CD44+, high aldehyde dehydrogenase activity (ALDH+) or could be enriched by mammosphere cultivation. These cells have been proven to be associated with tumor vascularization. Here we investigated the molecular mechanisms in VM activity of BCSCs. By periodic acid-Schiff or hematoxylin-eosin stain, we found that there were VM structures in two xenografted human breast cancer tissues established from CD24 -CD44+ or ALDH+ cells. Only ALDH+ or mammosphere-forming BCSCs could form tube structures on matrigel-coated surface as similar as microvascular endothelial cells. Inhibition of the phosphorylation of epidermal growth factor receptor (EGFR) by gefitinib or knockdown of EGFR by lentiviral shRNA abolished the in vitro VM activity of BCSCs. By quercetin treatment, a plant flavonoid compound which is known to suppress heat shock proteins, or siRNA-mediated gene silencing, both Hsp27 expression and VM capability of BCSCs were suppressed. Forced expression of phosphor-mimic form of Hsp27 in ALDH+ BCSCs could overcome the inhibitory effect of gefitinib. In conclusion, our data demonstrate that VM activity of BCSCs is mediated by EGF/Hsp27 signaling and targeting this pathway may benefit to breast cancer therapy.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalBiochimie
Volume104
Issue number1
DOIs
StatePublished - 09 2014

Keywords

  • Breast cancer
  • Cancer stem/progenitor cells
  • Epidermal growth factor
  • Heat shock protein 27
  • Vasculogenic mimicry

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