Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs
Article first published online: 16 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 123, Issue 11, pages 2473–2479, 1 December 2008
How to Cite
Goldoni, S. and Iozzo, R. V. (2008), Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs. Int. J. Cancer, 123: 2473–2479. doi: 10.1002/ijc.23930
- Issue published online: 24 SEP 2008
- Article first published online: 16 SEP 2008
- Manuscript Accepted: 4 AUG 2008
- Manuscript Received: 24 APR 2008
- small leucine-rich proteoglycans;
- EGF receptor;
- IGF-I receptor;
- cancer growth;
Decorin, the prototype member of the small leucine-rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFβ. Decorin also modulates the insulin-like growth factor receptor and the low-density lipoprotein receptor-related protein 1, which indirectly affects the TGFβ receptor pathway. When expressed in tumor xenograft-bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin. © 2008 Wiley-Liss, Inc.