Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression

Charles Saby, Emilie Buache, Sylvie Brassart-Pasco, Hassan El Btaouri, Marie-Pierre Courageot, Laurence Van Gulick, Roselyne Garnotel, Pierre Jeannesson and Hamid Morjani _

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Oncotarget. 2016; 7:24908-24927. https://doi.org/10.18632/oncotarget.8795

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Abstract

Charles Saby1, Emilie Buache1, Sylvie Brassart-Pasco2, Hassan El Btaouri3, Marie-Pierre Courageot3, Laurence Van Gulick1, Roselyne Garnotel2, Pierre Jeannesson1 and Hamid Morjani1

1 Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche (UFR) Pharmacie, Reims, France

2 Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche (UFR) Médecine, Reims, France

3 Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche (UMR) Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne, Unité de Formation et de Recherche (UFR) Sciences Exactes et Naturelles, Reims, France

Correspondence to:

Hamid Morjani, email:

Keywords: type I collagen, aging, cancer, discoidin domain receptor 2, cell proliferation, Gerotarget

Received: July 16, 2015 Accepted: April 10, 2016 Published: April 18, 2016

Abstract

Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).

We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.

In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2.


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