Oncogenic linear collagen vi of invasive breast cancer is induced by ccl5

Elizabeth Brett, Matthias Sauter, Éadaoin Timmins, Omid Azimzadeh, Michael Rosemann, Juliane Merl-Pham, Stefanie M. Hauck, Peter J. Nelson, Karl Friedrich Becker, Ilse Schunn, Aoife Lowery, Michael J. Kerin, Michael Atkinson, Achim Krüger, Hans Günther Machens, Dominik Duscher

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo.

Original languageEnglish
Article number991
JournalJournal of Clinical Medicine
Volume9
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Adipose derived stem cell
  • Border
  • CCL5
  • Collagen VI
  • Decellularization
  • Extracellular matrix
  • Invasion
  • Linear
  • Metastatic
  • Triple negative breast cancer

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