Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling

Commun Biol. 2021 Jun 24;4(1):780. doi: 10.1038/s42003-021-02308-6.


Breast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. The regulatory mechanisms of BCSC interactions with the vascular niche within the tumor microenvironment (TME) and their self-renewal are currently under extensive investigation. We have demonstrated the existence of an arteriolar niche in the TME of human BC tissues. Intriguingly, BCSCs tend to be enriched within the arteriolar niche in human estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the lysophosphatidic acid (LPA)/protein kinase D (PKD-1) signaling pathway, which promotes both arteriolar differentiation of ECs and self-renewal of CSCs likely via differential regulation of CD36 transcription. This study indicates that CSCs may enjoy blood perfusion to maintain their stemness features. Targeting the LPA/PKD-1 -CD36 signaling pathway may have therapeutic potential to curb tumor progression by disrupting the arteriolar niche and effectively eliminating CSCs.

Publication types

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

MeSH terms

  • Breast Neoplasms / pathology*
  • CD36 Antigens / analysis
  • Cell Communication
  • Cell Differentiation
  • Endothelial Cells / cytology
  • Female
  • Humans
  • Lysophospholipids / physiology*
  • Neoplastic Stem Cells / physiology*
  • Protein Kinase C / analysis
  • Protein Kinase C / physiology*
  • Signal Transduction / physiology
  • Stem Cell Niche / physiology*
  • Tumor Microenvironment


  • CD36 Antigens
  • Lysophospholipids
  • protein kinase D
  • Protein Kinase C
  • lysophosphatidic acid