Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 97, Issue -, Pages 174-185Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2015.10.016
Keywords
Small leucine-rich proteoglycan; Autophagy; Mitophagy; Angiogenesis; Endothelial cells; Receptor tyrosine kinases
Categories
Funding
- National Institutes of Health [RO1 CA39481, RO1 CA47282, RO1 CA164462]
- German Research Council [SFB 815, A5, SFB 1039, B2]
- Excellence Cluster ECCPS
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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. (C) 2015 Elsevier B.V. All rights reserved.
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