Extracellular matrix proteins and proteoglycans (ECM)

The extracellular matrix (ECM) is a complex, non-cellular network of proteins and carbohydrates, including collagens, proteoglycans, and glycoproteins, that provides essential structural and biochemical support to tissues (Frantz et al., 2010). Proteoglycans, such as aggrecan, syndecan, and glypican, are characterized by a core protein with attached glycosaminoglycan chains and are critical for regulating cell signaling, tissue hydration, and growth factor sequestration (Iozzo & Schaefer, 2015). In diseases like cancer and fibrosis, the ECM is often pathologically remodeled, leading to increased tissue stiffness and altered signaling that promotes tumor progression and organ dysfunction (Lu et al., 2012). Therapeutic strategies targeting the ECM include the use of enzymes like hyaluronidase and collagenase to degrade specific components, as well as inhibitors of ECM-modifying enzymes like lysyl oxidase (LOX) (Cox & Erler, 2011). For instance, hyaluronidase is used to increase the dispersion and absorption of other injected drugs by temporarily breaking down hyaluronan in the interstitial matrix (Wohlrab et al., 2014). Collagenase clostridium histolyticum is employed to treat conditions like Dupuytren's contracture by enzymatically disrupting collagen deposits (Hurst et al., 2009). While these approaches aim to improve drug delivery or reduce scarring, the ubiquitous nature of ECM proteins poses significant challenges for achieving tissue specificity and avoiding systemic toxicity (Nallanthighal et al., 2019).

Other names

Proteoglycans and other ECM proteinsExtracellular matrixMatrisomeGround substanceECM proteins

Enzymatic degradation of extracellular matrix components, inhibition of matrix assembly, or modulation of cell-matrix interactions.