title: Decorin as a multivalent therapeutic agent against cancer.
abstract: Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target-rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition, tumor cell mitophagy, and angiostasis. Decorin is also pro-inflammatory by modulating macrophage function and cytokine secretion. Decorin suppresses tumorigenic growth, angiogenesis, and prevents metastatic lesions in a variety of in vitro and in vivo tumor models. Therefore, decorin would be an ideal therapeutic candidate for combating solid malignancies.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Neill
authors.affiliation: Department of Pharmacology, Goethe University, 60590 Frankfurt, Germany.
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: renato.iozzo@jefferson.edu.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
mesh_terms: D000818:Animals; D001343:Autophagy; D058575:Decorin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism
chemical_list: D058575:Decorin; C512478:EGFR protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Angiogenesis; Autophagy; Endothelial cells; Mitophagy; Receptor tyrosine kinases; Small leucine-rich proteoglycan