Endogenous chemokines and growth factors as a local reservoir

The concept of endogenous chemokines and growth factors as a local reservoir refers to the physiological sequestration of signaling proteins within the extracellular matrix (ECM) and on cell-surface heparan sulfate proteoglycans (HSPGs) (Hynes, 2009, Science). This reservoir is primarily formed through the binding of heparin-binding domains on growth factors, such as Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF), and chemokines, such as CXCL12, to glycosaminoglycans like heparan sulfate (Bishop et al., 2007, Nature). This interaction serves several critical functions: it protects the proteins from proteolytic degradation, establishes stable concentration gradients necessary for directed cell migration (chemotaxis), and regulates the timing of factor release to their respective receptors (Proudfoot, 2006, Biochemical Society Transactions). In pathological states like cancer, the remodeling of this reservoir via enzymes like heparanase can lead to a sudden surge in pro-angiogenic and pro-metastatic signals (Vlodavsky et al., 2012, Matrix Biology). Therapeutic approaches often aim to either stabilize this reservoir to prevent pathological signaling or to mimic its properties in tissue engineering to promote localized healing using heparin mimetics or heparanase inhibitors.

Other names

Extracellular matrix reservoirECM-bound growth factor poolHeparan sulfate proteoglycan (HSPG) reservoirSequestration of signaling moleculesGlycosaminoglycan-bound signaling pool

Modulation of the sequestration and release of signaling molecules from the extracellular matrix to regulate local receptor activation.