early genetic studies suggest that a lack of decorin is permissive for tumor development . more specifically , crossing decorin - null mice with the p53-null mice caused early lethality of the double mutant animals because of massive organ infiltration by t - cell lymphoma .
a more recent publication from our group demonstrates that decorin can indeed act as a tumor suppressor gene in the intestinal epithelium .
we found that approximately 30% of decorin - null mice developed spontaneous intestinal tumors , and this process was accelerated and amplified by subjecting the decorin - null mice to a western diet enriched in fat and low in calcium and vitamin d. tumor development involved down - regulation of p21 and p27 and up - regulation of -catenin signaling .
notably , decorin binds directly to epidermal growth factor receptor ( egfr ) and down - regulates its activity , as well as the activity of other members of the erbb family , .
these receptors are overexpressed and/or mutated in many cancers , driving tumor progression. decorin competes with egf for receptor binding on the surface of tumor cells . after binding decorin ,
the receptor dimerizes and subsequently undergoes caveolin - mediated internalization and degradation in the lysosomes .
decorin inhibits tumor cell proliferation by evoking a signaling cascade distinct from egf , possibly by inducing a different egfr confirmation and selectively activating phosphotyrosines in the receptor autophosphorylation domain .
in addition , decorin suppresses the activity of the erbb2 and erbb4 receptors via degradation , .
decorin also interacts with met , the hepatocyte growth factor receptor , and induces transient receptor activation , recruitment of the e3 ubiquitin ligase c - cbl , and rapid intracellular degradation of the receptor .
furthermore , decorin suppresses intracellular levels of -catenin , a key downstream effector of met , and inhibits cell migration and growth .
thus , by antagonistically targeting multiple tyrosine kinase receptors , decorin reduces primary tumor development and progression .
another important step in cancer progression is angiogenesis , the process whereby new vessels grow from preexisting blood vessels .
notably , by binding transforming growth factor- ( tgf- ) , decorin interacts with tgf- , preventing tgf- from binding to its receptor , and therefore plays a significant role in tumor progression and angiogenesis .
decorin can also play a proangiogenic role by facilitating endothelial cell adhesion and migration on type i collagen . specifically ,
decorin mediates adhesion by binding to 21 integrin and promoting the integrin - collagen interaction .
interestingly , decorin mediates endothelial cell migration by modulating insulin - like growth factor ( igf)/insulin receptor 1 ( ir1 ) signaling , confirming that the decorin / igf-1r interaction plays a role in angiogenesis .
two potential mechanisms may underlie these antiangiogenic activities : interfering with thrombospondin-1 , or suppressing the production of endogenous vascular endothelial growth factor ( vegf ) in tumor cells , which in turn attenuates migration and capillary - like formation of endothelial cells .
a more recent study showed that decorin antagonizes the angiogenic network in breast cancer cells via inhibition of met , hypoxia inducible factor-1 ( hif-1 ) , and vegfa , as well as induction of the angiostatic proteins thrombospordin-1 and tissue inhibitor of metallo - proteinases-3 ( timp3 ) .
thus , one of decorin 's roles in the microenvironment is the modulation of angiogenesis , albeit in a cell - specific context , upon the physiological or pathological stimulation .
the involvement of decorin in metastasis is still open to investigation and is far from being resolved .
however , because of its functions in the microenvironment and extracellular matrix , we postulate that decorin plays a significant role in tumor metastasis .
loss of e - cadherin promotes metastasis by inducing cancer cell disaggregation , activating specific downstream signal transduction pathways , and causing epithelial - mesenchymal transition ( emt ) , which facilitates metastasis .
our recent studies in decorin - null mice and increasing decorin expression in human colon cancer cells in vitro have demonstrated an interaction between decorin and e - cadherin , which may underlie another mechanism of the antimigratory and antimetastatic actions of decorin in colorectal carcinoma , , , .
interestingly , decorin has also been implicated in down - regulating the e - cadherin binding partner -catenin in vitro , in vivo , and in xenograft models , , .
accumulating evidence suggests that the stromal - epithelial interaction is important for tumor progression and metastasis .
tumor stroma represents the surrounding normal ecm or the microenvironment of the tumor cell through which stromal and tumor cells talk .
reduced decorin levels in cancer tissues might alter several signal pathways due to the well known interactions between decorin and the tyrosine kinase receptors described above .
alternatively , one could postulate that abundant expression of decorin may lead to an  organized 
indeed , there is a regulation among decorin and stromal components including matrix metalloproteinases ( mmps ) .
an earlier study also indicated decorin may affect signaling via chemokine receptor cxcr4 , possibly affecting metastasis .
decorin syngerizes with carboplatin to inhibit ovarian cancer cell growth but antagonizes the effects of carboplatin and gemcitabine on pancreatic cancer cells .
considering that decorin can be administered alone or concomitantly with a variety of compounds , we anticipate that decorin will attract more interest in the future as an anticancer therapeutic agent .
administration of decorin core protein in an a431 squamous carcinoma model resulted in decorin localizing specifically within the tumor , antagonizing egfr activity , and inducing apoptosis .
systemic injection of decorin reduced breast tumor growth and metabolism and halted metastatic spread to the lungs .
earlier studies also show that decorin delivered by adenovirus slowed the growth of lung , squamous , and colon carcinoma tumor xenografts in immune - compromised mice , .
adenovirus - delivered decorin also slowed the growth of mammary adenocarcinoma and prevented metastatic spreading to the lungs by down - regulating erbb2 receptor levels .
notably , the size of the tumors in that model was directly proportional to how early and how much decorin was expressed .
the finding that decorin antagonizes primary tumor growth and metastasis in vivo raises hope for clinical application .
decorin might be utilized in the near future as an adjunct  protein therapeutic  for solid tumors in which receptor tyrosine kinases play a key role .
slrps , including decorin , are characterized by a protein core containing leucine repeats with a glycosaminoglycan chain , consisting of either chondroitin sulfate or dermatan sulfate .
in particular , highly metastatic cell lines show the prevalence of chondroitin sulfate , but not dermatan sulfate .
future studies should also be undertaken to elucidate the functional interaction between decorin and existing anticancer chemotherapeutics to evaluate potential limitations .
because decorin expression is altered in several types of cancer , it is considered a possible prognostic marker in cancer patients .
reduced decorin levels were associated with poor prognosis in node - negative , invasive breast cancer and some soft - tissue tumors . specifically , low decorin levels correlated with large primary breast tumor burden , high risk of early recurrence , and overall poor prognosis .
breast cancer patients with tumors high in egfr and low in decorin had an even worse outcome .
this reinforces the notion that decorin is a key player in egfr signal modulation in vivo .
low decorin levels in liposarcomas and malignant peripheral nerve sheath tumors were also associated with low disease - free survival and overall survival rates .
a recent study suggested that stromal decorin expression provides additional prognostic value in breast cancer when used with established primary markers .
we foresee that decorin will attract more interest in the future as a promising prognostic marker for cancer patients .
decorin 's biological activity is rather complex ; it regulates multiple processes in the extracellular matrix and in tumor cells ( figure 1 ) .
studies in mouse models and cancer patients suggest that decorin plays an important role throughout the tumor growth and development process and may be a promising antitumor agent . in vivo studies with more tumor models
decorin interacts with egfr , erbb , c - met , igf - ir , tgfr , and 21 , respectively , leads to induction of p21waf1 , signaling modulation , proteasome deregulation , activation of pi3k / akt / mtor and pi3k / smad signaling , finally causes degradation of endocytosis , inhibition of tumor cell growth , migration , angiogenesis , endothelial cell proliferation , and motility , exerting tumor suppressor .
egfr , epidermal growth factor receptor ; igf - ir , insulin - like growth factor - insulin receptor ; tgf- , transforming growth factor- ; 21 , integrin alpha2-beta1 ; pi3k , phosphatidylinositol 3-kinase ; mtor , mammalian target of rapamycin .
 decorin is a member of the extracellular matrix small leucine - rich proteoglycans family that exists and functions in stromal and epithelial cells . 
 accumulating evidence suggests that decorin affects the biology of various types of cancer by directly or indirectly targeting the signaling molecules involved in cell growth , survival , metastasis , and angiogenesis . 
 more recent studies show that decorin plays important roles during tumor development and progression and is a potential cancer therapeutic agent . in this article , we summarize recent studies of decorin in cancer and discuss decorin 's therapeutic and prognostic value . 
Decorin in Tumor Development and Progression
Decorin in Tumor Angiogenesis
Decorin in Tumor Metastasis
Decorin as a Potential Anticancer Agent
Decorin as a Biomarker for Prognosis
Concluding Remarks