Decorin: A Growth Factor Antagonist for Tumor Growth Inhibition

Figure 2

Decorin interacts with multiple growth factor signaling pathways crucial for cancer growth. Schematic drawing of the molecular structure of decorin (DCN). All four domains, I–IV, of decorin core protein are indicated. DCN has a monomeric protein core and a single chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain. Structurally, it has a domain of tandem leucine-rich repeats (LRRs), flanked on both sides by two cysteine-rich regions. DCN interacts with a wide set of different signaling molecules; among them are different isoforms of transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), and ErbB1–4 receptor tyrosine kinases, myostatin (MyoS), connective tissue growth factor/CCN2 (CTGF), thrombospondin (Thbs), collagen (Col), and fibronectin (FN), implicated in cancer progression. The active/binding sites of DCN for TGF-β, CCN2, c-Met, and EGFR neutralization/binding all reside in different parts of the DCN molecule. Thus, in theory, a single DCN molecule could simultaneously sequester multiple important mediators of tumor growth and antagonize multiple signaling pathways crucial for tumor growth and progression. Thus, owing to this multifunctionality, DCN may exert its anticancer effects through multiple molecular approaches that all contribute to varying degree to its biological effects on cancer cells and tumor environment.