Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.
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 TGFbeta. Decorin also modulates the insulin-like growth factor receptor and the low-density lipoprotein receptor-related protein 1, which indirectly affects the TGFbeta 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.
Goldoni
Silvia
S
Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Iozzo
Renato V
RV
D020816:Amino Acid Motifs; D000818:Animals; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D000090263:Leucine-Rich Repeat Proteins; D009369:Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011509:Proteoglycans / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction
C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011509:Proteoglycans; D007930:Leucine