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Brett, E.* ; Sauter, M.* ; Timmins, E.* ; Azimzadeh, O. ; Rosemann, M. ; Merl-Pham, J. ; Hauck, S.M. ; Nelson, P.J.* ; Becker, K.F.* ; Schunn, I.* ; Lowery, A.* ; Kerin, M.J.* ; Atkinson, M.J. ; Krueger, A.* ; Machens, H.* ; Duscher, D.*

Oncogenic linear collagen VI of invasive breast cancer is induced by CCL5.

J. Clin. Med. 9:991 (2020)

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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.

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