Oncogenic Linear Collagen VI of Invasive Breast Cancer Is Induced by CCL5.

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

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.

COLLAGEN; BREAST cancer; TRIPLE-negative breast cancer; EXTRACELLULAR matrix; STEM cells

Journal of Clinical Medicine, 2020, Vol 9, Issue 4, p991

2077-0383

Academic Journal

10.3390/jcm9040991