The tumor matrix together with inflammation and autophagy are crucial regulators of cancer development. Embedded in the tumor stroma are numerous proteoglycans which, in their soluble form, act as danger-associated molecular patterns (DAMPs). By interacting with innate immune receptors, the Toll-like receptors (TLRs), DAMPs autonomously trigger aseptic inflammation and can regulate autophagy. Biglycan, a known danger proteoglycan, can regulate the cross-talk between inflammation and autophagy by evoking a switch between pro-inflammatory CD14 and pro-autophagic CD44 co-receptors for TLRs. Thus, these novel mechanistic insights provide some explanation for the plethora of reports indicating that the same matrix-derived DAMP acts either as a promoter or suppressor of tumor growth. In this review we will summarize and critically discuss the role of the matrix-derived DAMPs biglycan, hyaluronan, and versican in regulating the TLR-, CD14- and CD44-signaling dialogue between inflammation and autophagy with particular emphasis on cancer development.
Keywords: Biglycan; Hyaluronan; Inflammation; Toll-like receptor; Versican.
Copyright © 2019 Elsevier Ltd. All rights reserved.