When cells are under stress, components of the extracellular matrix can be released and initiate signaling through receptors on the cell surface. The proteoglycan decorin is one such matrix component, and it promotes inflammatory signaling in response to bacterial infection or tumor growth. Merline et al. present evidence for two mechanisms by which decorin can influence inflammatory responses. One is initiated through binding to Toll-like receptors 2 and 4, which leads to increased production of programmed cell death 4 (PDCD4), a tumor suppressor and proinflammaory protein that interacts with various proteins and RNAs. Decorin also appeared to promote accumulation of PDCD4 by inhibiting signaling through transforming growth factor–β receptors. Consistent with such regulation, decorin accumulated in plasma from human patients undergoing septic response to bacterial infection and promoted inflammation in a mouse cancer model, thus inhibiting tumor growth.
Sci. Signal. 4, ra75 (2011).