scholarly journals Discoidin domain receptor 2 regulates neutrophil chemotaxis in 3D collagen matrices

Blood ◽  
2013 ◽  
Vol 121 (9) ◽  
pp. 1644-1650 ◽  
Author(s):  
Philippe V. Afonso ◽  
Colin P. McCann ◽  
Senta M. Kapnick ◽  
Carole A. Parent
Keyword(s):  
Neutrophil Chemotaxis ◽  
Chemotactic Peptide ◽  
Directional Migration ◽  
Collagen Matrices ◽  
Discoidin Domain Receptor ◽  
Key Points ◽  
3D Collagen ◽  
Discoidin Domain Receptor 2

Key Points DDR2 regulates the directional migration of neutrophils in 3D collagen matrices, but not on 2D surfaces. DDR2 regulates directionality through increased metalloproteinase secretion and generation of collagen-derived chemotactic peptide gradients.

scholarly journals Discoidin domain receptor 2 regulates the adhesion of fibroblasts to 3D collagen matrices

2013 ◽  
Vol 31 (5) ◽  
pp. 1113-1118 ◽  
Author(s):  
DAEHWAN KIM ◽  
EUNAE YOU ◽  
NA YOUNG MIN ◽  
KWANG-HO LEE ◽  
HYOUNG KYU KIM ◽  
...  
Keyword(s):  
Collagen Matrices ◽  
Discoidin Domain Receptor ◽  
3D Collagen ◽  
Discoidin Domain Receptor 2

scholarly journals Endothelial lumen signaling complexes control 3D matrix–specific tubulogenesis through interdependent Cdc42- and MT1-MMP–mediated events

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5259-5269 ◽  
Author(s):  
Anastasia Sacharidou ◽  
Wonshill Koh ◽  
Amber N. Stratman ◽  
Anne M. Mayo ◽  
Kevin E. Fisher ◽  
...  
Keyword(s):  
Tube Formation ◽  
Dominant Negative ◽  
Collagen Matrices ◽  
Signaling Complex ◽  
Vascular Morphogenesis ◽  
Cytoplasmic Tails ◽  
3D Matrix ◽  
Dependent Signal ◽  
3D Collagen ◽  
Membrane Type

Abstract Here, we define an endothelial cell (EC) lumen signaling complex involving Cdc42, Par6b, Par3, junction adhesion molecule (Jam)–B and Jam-C, membrane type 1–matrix metalloproteinase (MT1-MMP), and integrin α2β1, which coassociate to control human EC tubulogenesis in 3D collagen matrices. Blockade of both Jam-B and Jam-C using antibodies, siRNA, or dominant-negative mutants completely interferes with lumen and tube formation resulting from a lack of Cdc42 activation, inhibition of Cdc42-GTP–dependent signal transduction, and blockade of MT1-MMP–dependent proteolysis. This process requires interdependent Cdc42 and MT1-MMP signaling, which involves Par3 binding to the Jam-B and Jam-C cytoplasmic tails, an interaction that is necessary to physically couple the components of the lumen signaling complex. MT1-MMP proteolytic activity is necessary for Cdc42 activation during EC tube formation in 3D collagen matrices but not on 2D collagen surfaces, whereas Cdc42 activation is necessary for MT1-MMP to create vascular guidance tunnels and tube networks in 3D matrices through proteolytic events. This work reveals a novel interdependent role for Cdc42-dependent signaling and MT1-MMP–dependent proteolysis, a process that occurs selectively in 3D collagen matrices and that requires EC lumen signaling complexes, to control human EC tubulogenesis during vascular morphogenesis.

scholarly journals Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices

2015 ◽  
Vol 101 ◽  
pp. 72-81 ◽  
Author(s):  
Hyojin Kim ◽  
Nutan Prasain ◽  
Sasidhar Vemula ◽  
Michael J. Ferkowicz ◽  
Momoko Yoshimoto ◽  
...  
Keyword(s):  
Cord Blood ◽  
Human Platelet ◽  
Three Dimensional ◽  
Platelet Lysate ◽  
Human Cord Blood ◽  
Collagen Matrices ◽  
Human Platelet Lysate ◽  
3D Collagen

scholarly journals Discoidin Domain Receptor 2 Mediates Lysophosphatidic Acid-Induced Ovarian Cancer Aggressiveness

2021 ◽  
Vol 22 (10) ◽  
pp. 5374
Author(s):  
Bo Young Jeong ◽  
Kyung Hwa Cho ◽  
Se-Hee Yoon ◽  
Chang Gyo Park ◽  
Hwan-Woo Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Lysophosphatidic Acid ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Invasion ◽  
Discoidin Domain Receptor ◽  
Cancer Aggressiveness ◽  
Discoidin Domain Receptor 2

Lysophosphatidic acid (LPA), a bioactive lipid produced extracellularly by autotaxin (ATX), has been known to induce various pathophysiological events, including cancer cell invasion and metastasis. Discoidin domain receptor 2 (DDR2) expression is upregulated in ovarian cancer tissues, and is closely associated with poor clinical outcomes in ovarian cancer patients. In the present study, we determined a critical role and signaling cascade for the expression of DDR2 in LPA-induced ovarian cancer cell invasion. We also found ectopic expression of ATX or stimulation of ovarian cancer cells with LPA-induced DDR2 expression. However, the silencing of DDR2 expression significantly inhibited ATX- and LPA-induced ovarian cancer cell invasion. In addition, treatment of the cells with pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and mTOR abrogated LPA-induced DDR2 expression. Moreover, we observed that HIF-1α, located downstream of the mTOR, is implicated in LPA-induced DDR2 expression and ovarian cancer cell invasion. Finally, we provide evidence that LPA-induced HIF-1α expression mediates Twist1 expression to upregulate DDR2 expression. Collectively, the present study demonstrates that ATX, and thereby LPA, induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.

Role of Discoidin Domain Receptor 2 in Craniofacial Bone Regeneration

2021 ◽  
pp. 002203452110074
Author(s):  
A. Binrayes ◽  
C. Ge ◽  
F.F. Mohamed ◽  
R.T. Franceschi
Keyword(s):  
Bone Regeneration ◽  
Healing Process ◽  
Congenital Defects ◽  
Calvarial Bone ◽  
Discoidin Domain Receptor ◽  
Skeletal Defects ◽  
Discoidin Domain Receptor 2 ◽  
Collagen Receptor ◽  
Deficient Mice

Bone loss caused by trauma, neoplasia, congenital defects, or periodontal disease is a major cause of disability and human suffering. Skeletal progenitor cell–extracellular matrix interactions are critical for bone regeneration. Discoidin domain receptor 2 (DDR2), an understudied collagen receptor, plays an important role in skeletal development. Ddr2 loss-of-function mutations in humans and mice cause severe craniofacial and skeletal defects, including altered cranial shape, dwarfing, reduced trabecular and cortical bone, alveolar bone/periodontal defects, and altered dentition. However, the role of this collagen receptor in craniofacial regeneration has not been examined. To address this, calvarial subcritical-size defects were generated in wild-type (WT) and Ddr2-deficient mice. The complete bridging seen in WT controls at 4 wk postsurgery was not observed in Ddr2-deficient mice even after 12 wk. Quantitation of defect bone area by micro–computed tomography also revealed a 50% reduction in new bone volume in Ddr2-deficient mice. Ddr2 expression during calvarial bone regeneration was measured using Ddr2-LacZ knock-in mice. Expression was restricted to periosteal surfaces of uninjured calvarial bone and, after injury, was detected in select regions of the defect site by 3 d postsurgery and expanded during the healing process. The impaired bone healing associated with Ddr2 deficiency may be related to reduced osteoprogenitor or osteoblast cell proliferation and differentiation since knockdown/knockout of Ddr2 in a mesenchymal cell line and primary calvarial osteoblast cultures reduced osteoblast differentiation while Ddr2 overexpression was stimulatory. In conclusion, Ddr2 is required for cranial bone regeneration and may be a novel target for therapy.

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