2. Academic Validation
  3. Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells

Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells

  • bioRxiv. 2024 Aug 2:2024.08.02.606061. doi: 10.1101/2024.08.02.606061.
Natalia Krawczynska 1 2,  Yu Wang 1,  Ki Lim 1,  Anasuya Das Gupta 1,  Adam Lenczowski 1,  Marwan Abughazaleh 1,  Shruti V Bendre 1,  Lara I Kockaya 1,  Claire P Schane 1,  Yifan Fei 1,  Alvaro G Hernandez 3,  Jenny Drnevich 3,  Jefferson Chan 2 4 5,  Lawrence W Dobrucki 2 5 6 7,  Marni D Boppart 2 8 9,  Julie Ostrander 10 11,  Erik R Nelson 1 2 5 12 13
Affiliations

Affiliations

  • 1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 2 Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 3 Roy J. Carver Biotechnology Center, The University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 4 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 5 Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 6 Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 7 Carle-Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 8 Department of Health and Kinesiology, University of Illinois Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 9 Carl R. Woese Institute for Genomic Biology- Regenerative Biology & Tissue Engineering, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 10 Masonic Cancer Center, University of Minnesota, Minneapolis Minnesota, 55455 USA.
  • 11 Department of Medicine (Division of Hematology, Oncology, and Transplantation), University of Minnesota, Minneapolis Minnesota, 55455 USA.
  • 12 Carl R. Woese Institute for Genomic Biology- Anticancer Discovery from Pets to People, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
  • 13 Division of Nutritional Sciences, University of Illinois Urbana-Champaign, University of Illinois at Urbana-Champaign, Urbana Illinois, 61801 USA.
PMID: 39131340 DOI: 10.1101/2024.08.02.606061
Abstract

Small extracellular vesicles (sEVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME). Here, we investigate the mechanisms by which sEVs derived from neutrophils treated with the Cholesterol metabolite, 27-hydroxycholesterol (27HC), influence breast Cancer progression. sEVs released from 27HC treated neutrophils enhance epithelial-mesenchymal transition (EMT) and stem-like properties in breast Cancer cells, resulting in loss of adherence, increased migratory capacity and resistance to cytotoxic chemotherapy. Decreased MicroRNAs (miRs) within the sEVs resulted in activation of the Wnt/β-catenin signaling pathway in recipient cells and suggest that this may be a predominant pathway for stem-like phenotype and EMT. Our findings underscore a novel mechanism by which 27HC-modulated neutrophils contribute to breast Cancer pathophysiology through EV-mediated intercellular communication, suggesting potential therapeutic targets in Cancer treatment.

Keywords

27-hydroxycholesterol; EMT; breast cancer; extracellular vesicle; neutrophil; stemness.

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