Table 2.

Select examples of extracellular matrix modulation of growth factor activities

ECM–Growth Factor Interaction	Example	Consequence
ECM binding to growth factor	Binding of FGF-2 and VEGF to heparin sulfate10,11	Binding of growth factor to ECM facilitates/enhances signaling
	Binding of TGFβ1 to decorin, beta-glycan, biglycan, collagens, fibrillin5,7,12	Sequestration and inactivation of TGFβ by matrix molecules
	Binding of FGF to fibrin and fibrinogen6	Protection of growth factor from degradation
Activation of growth factors from a latent form	TSP-1 activation of latent TGFβ8	ECM component directly activates latent growth factor
	Stiffness of matrix activates TGFβ9,13	Activation of TGFβ mediated by the stiff ECM through integrin sensing or enhanced stimulation via the PI3/Akt signaling pathway
Matrikine–growth factor receptor interaction	Tenascin-C and laminin bind to EGF receptors14	Matrikine induced signaling through growth factor receptor binding
ECM–integrin interaction-mediated growth factor signaling	Expression of αvβ3 is required for TNFα and VEGF induced angiogenesis15	ECM modulation of integrin expression/activation modulates growth factor signaling

 ECM, extracellular matrix; FGF, fibroblast growth factor; VEGF, vascular endothelial growth factor; TGFβ, transforming growth factor beta; TSP, thrombospondins; EGF, epidermal growth factor; TNF, tumor necrosis factor.