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Regulation of breast carcinoma cell proliferation and apoptosis by type I collagen aging and 3D confinement involves differential activation of DDR1
Saby, Charles; Rammal, Hassan; Magnien, Kevin et al.
2016EACR - GOODBYE FLAT BIOLOGY: MODELS, MECHANISMS AND MICROENVIRONMENT
 

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Keywords :
cancer; 3D; model
Abstract :
[en] During breast carcinoma development, cells are confronted to a type I collagen-rich environment which induces anti-proliferative and pro-apoptotic effects (Maquoi et al., Oncogene, 2012). These effects occurred only in 3D cell matrix and involved Discoidin Domain Receptor 1 (DDR1) but not β1 integrin (Assent et al., PlosOne, 2015). During aging, type I collagen undergoes post-translational modifications which have a detrimental effect on type I collagen fibrillar organization (Aït-Belkacem, J Biomed Optics, 2012 ; Guilbert et al., Oncotarget, 2016). This property is well known to be requested to activate DDR1. Here, we address the effect of type I collagen aging on cell proliferation inhibition and apoptosis induction in breast carcinoma cells in 3D cell confinement system. Type I collagen was extracted from tail tendons of 2 months (adult) and 2 years (old) rats, and MCF-7 and ZR-75-1 cells were used as an experimental model. We provide evidence for a decrease in cell proliferation by adult collagen but not by old one. This effect involves a higher phosphorylation of DDR1 by adult collagen when compared to the old one. Inhibition of DDR1 kinase activity by the specific inhibitor DDR1-IN-1 induced an increase in cell proliferation to a level similar to that observed in old collagen. An increase in cell proliferation was also observed using siRNA targeting DDR1 mRNA. At the opposite of old collagen, adult collagen was also able to trigger apoptosis by inducing an increase in expression of the pro-apoptotic protein (BIK). Inhibition of DDR1 kinase activity induced a decrease in BIK expression and apoptosis. Our data support the concept that aging contributes to the loss of the growth suppression and apoptotic effect of collagen on breast carcinoma, but only in 3D cell confinement model, by inactivating the DDR1-BIK signaling axis via a downregulation of DDR1 activation.
Disciplines :
Oncology
Author, co-author :
Saby, Charles;  Université de Reims > Faculté de Pharmacie
Rammal, Hassan;  Université de Reims > Faculté de Pharmacie
Magnien, Kevin;  Université de Reims > Faculté de Pharmacie
Pasco-Brassart, Sylvie;  Université de Reims > Faculté de Médecine
Maquoi, Erik  ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Jeannesson, Pierre;  Université de Reims > Faculté de Pharmacie
Morjani, Hamid;  Université de Reims > Faculté de Médecine
Language :
English
Title :
Regulation of breast carcinoma cell proliferation and apoptosis by type I collagen aging and 3D confinement involves differential activation of DDR1
Publication date :
October 2016
Event name :
EACR - GOODBYE FLAT BIOLOGY: MODELS, MECHANISMS AND MICROENVIRONMENT
Event organizer :
EACR - European Association for Cancer Research
Event place :
Berlin, Germany
Event date :
02/10/2016 au 05/10/2016
Audience :
International
Available on ORBi :
since 10 October 2016

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