Decorin regulates endothelial cell-matrix interactions during angiogenesis

Figures & data

Figure 1 Decorin influences cell-matrix interactions through multiple mechanisms. Decorin signals through the IGF-IR via the core protein moiety (grey diamond), and may simultaneously interact with the α2 subunit (cross-hatched subunit) of α2β1 integrin via the GAG moiety (wavy black line) (A). Activation of Rac through IGF-IR enhances motility by modulating cytoskeleton dynamics and may influence α2β1 integrin activity for collagen I through inside-out signalling (B). Decorin induces large, peripheral vinculin (grey oval)-positive focal adhesions by signalling through IGF-IR and/or α2β1 integrin (C and D). Decorin could also directly influence α2β1 integrin activity through binding to the α2 subunit and/or simultaneous interactions with collagen I (thick wavy black line) through the core protein. Collagen I interacts with the A-domain (white circle) of the α2 subunit at a site distinct to that of decorin (D). In summary, activation of IGF-IR, Rac and modulation of α2β1 integrin affinity for collagen I by decorin modulates cell-matrix interactions and contributes to enhanced motility and tubulogenesis in a collagen I environment.

Table 1 Summary of the key functions of decorin in controlling cell behaviour

Cell type	Function	Decorin addition	Environment/Mechanism	References
Endothelial (HUVEC derived)	Enhanced tubulogenesis	Overexpression	Collagen I lattices, enhanced survival potentially IGF-IR mediated	6, 18
Mouse cerebral endothelial cells	Enhanced tubulogenesis	Overexpression	Matrigel substrate, EGFR activation leads to VEGF upregulation	8
HUVEC	No effect on tubulogenesis	Exogenous	Matrigel substrate	9
HUVEC	Inhibited tubulogenesis	Exogenous	Matrigel substrate, growth factor induced	10
HUVEC, HDMEC	Inhibited tubulogenesis	Substrate	Collagen I lattice overlay	7
HUVEC	Minimal adhesion	Substrate	Decorin substrate	7
HUVEC	Inhibited adhesion	Exogenous	Collagen I and fibronectin	10
HUVEC	Inhibited migration	Exogenous	VEGF-mediated chemotaxis through gelatin	10
Endothelial (HUVEC derived)	Enhanced adhesion	Exogenous	Collagen I, fibronectin	17
BAE	Inhibited migration	Overexpression	Collagen I, enhanced fibronectin fibrilllogenesis by decorin	12
Endothelial (HUVEC derived)	Enhanced motility	Exogenous	Collagen I, Decorin activates IGF-IR/Rac-1 and α2β1 integrin activity	17
Human lung fibroblast	Enhanced motility	Exogenous	Decorin activates Rho GTPases, mediators of motility	20
Human foreskin fibroblast	Inhibited adhesion	Exogenous	Decorin GAG moiety competes with CD44 for binding to collagen XIV	14
Mouse Fibroblast (3T3)	Inhibited adhesion	Exogenous	Decorin competes with cells for interaction with thrombospondin at the cell-binding domain	15
Human fibroblast	Inhibits adhesion	Exogenous	Decorin GAG competes with cell-surface heparin-sulphate for interaction with fibronectin	16
Platelets	Supported adhesion	Substrate	Decorin interacts with, and signals through α2β1 integrin on platelets	19

Decorin has been demonstrated to influence cell adhesion and motility, in particular, its influence on endothelial cell adhesion, migration and tube formation is controversial, and is the main focus of this table. Some additional key effects of decorin on fibroblast and platelet adhesion and motility are also summarised. In each case, the extracellular matrix environment in which the assay was conducted is shown, and where known, the proposed mechanism is stated.

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