Proteoglycans in health and disease: novel regulatory signaling mechanisms evoked by the small leucine-rich proteoglycans

Abstract

The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically assess their roles in cancer and innate immunity.

Fig. 1

Schematic representation of decorin effects as an antiproliferative (left panel) and proliferative (right panel) molecule. In most cancer cells so far investigated, decorin causes a downregulation of EGFR and Met with consequent activation of p21 and caspase-3, which leads to apoptosis. Decorin also interferes with the non-canonical β-catenin pathway via the Met receptor. In normal cells such renal tubular epithelial cells, decorin evokes a pro-survival and proliferative response via the IGF-IR and downstream signaling. Please, refer to the text for additional information.

Fig. 2

Schematic representation of biglycan and lumican effects on the innate immune system. Please, refer to the text for detailed information.