Small leucine-rich proteoglycans, at the crossroad of cancer growth and inflammation

Decorin causes autophagy in endothelial cells via Peg3

“…5A) to VEGFR2 ectodomain Ig [1][2][3][4][5][6][7] . Moreover, immobilized decorin bound with similar affinity to soluble VEGFR2 Ig [1][2][3][4][5][6][7] (Fig. 5B), and its binding to VEGFR2 could be displaced efficiently by VEGFA (IC 50 ∼50 nM) (Fig.…”

“…Many SLRPs, including decorin and biglycan, regulate a variety of vital biological processes, especially via their innate ability to bind collagen type I and ultimately regulate fibrillogenesis and bioavailability of various growth factors (3). However, many recent studies have broadened our view of decorin from a specialized collagen-bound factor and regulator of matrix assembly to that of a soluble multifunctional signaling proteoglycan (4,5). For example, circulating decorin has been detected in the plasma of normal volunteers and found to be elevated in diabetic (6) and septic patients (7).…”

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

“…Upon tissue stress or injury, matrix components will be released and turn into signaling molecules. 12,18,19 Among this large group of ECM components, only a few, such as biglycan, 14 decorin, 16 hyaluronan, 20 versican, 21 tenascin-C, 22 fibrinogen and heparan sulfate fragments, 23 are capable of interacting with PRRs, thereby alerting the innate immune system to impending tissue damage. These mechanisms give rise to a rapid response reaction without the need for de novo synthesis of danger molecules.…”

“…Decorin is capable of binding to four different receptor tyrosine kinases (RTKs), including the epidermal growth factor receptor (EGFR), 34 insulin-like growth factor-1 receptor (IGF-IR), [35][36][37][38] Met 39 and vascular endothelial growth factor receptor 2 (VEGFR2), 40 thereby impacting on fibrogenesis, 19 tumor growth and metastatic spreading. 12,41,42 A summary of recent data demonstrating the intricacy of decorin signaling, which links innate immunity, inflammation and tumor growth 16 is provided below.…”

“…2 Non-pathogenmediated inflammation is an important characteristic of atherosclerosis, tumorigenesis, gout, myocardial infarction, stroke and several autoimmune diseases (e.g., systemic lupus erythematosus). 2,11,12 With the high incidence of sterile inflammatory diseases, there is a considerable unmet medical need to resolve the mechanisms of innate immune activation in the absence of microbial pathogens.…”