More than matrix: The multifaceted role of decorin in cancer

Feugaing, David Denis Sofeu; Götte, Martin; Viola, Manuela

doi:10.1016/j.ejcb.2012.08.004

Cited by 98 publications

(100 citation statements)

References 129 publications

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“…This implies that decorin is a mesenchyme-specific gene product and that it exerts its effects in a paracrine fashion on endothelial and epithelial cells including cancer cells. Functionally, soluble and matrix-bound decorin modulate various biological processes including collagen fibrillogenesis, wound healing, myogenesis, bone physiology, stem cell biology, immunity, angiogenesis and fibrosis (Brandan and Gutierrez, 2013; Chen and Birk, 2013; Dunkman et al, 2013; Ichii et al, 2012; Neill et al, 2013; Neill et al, 2012a; Reed and Iozzo, 2002; Robinson et al, 2005; Seidler et al, 2011; Sofeu Feugaing et al, 2013; Zhang et al, 2009). Initially identified as a natural inhibitor of transforming growth factor-β (Ruoslahti and Yamaguchi, 1991; Yamaguchi et al, 1990), soluble decorin is emerging as a pan-RTK inhibitor targeting a multitude of RTKs with various affinity, including EGFR, Met, IGF-IR, VEGFR2 and PDGFR (Baghy et al, 2013; Buraschi et al, 2013; Goldoni et al, 2009; Iozzo, 1999; Iozzo et al, 2011; Khan et al, 2011; Morrione et al, 2013; Nikitovic et al, 2012; Schaefer and Iozzo, 2012; Schaefer et al, 2007; Schonherr et al, 2005; Seidler, 2012).…”

Section: Introductionmentioning

confidence: 99%

Decorin deficiency promotes hepatic carcinogenesis

et al. 2014

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Hepatocellular carcinoma represents one of the most-rapidly spreading cancers in the world. In the majority of cases, an inflammation-driven fibrosis or cirrhosis precedes the development of the tumor. During malignant transformation, the tumor microenvironment undergoes qualitative and quantitative changes that modulate the behavior of the malignant cells. A key constituent for the hepatic microenvironment is the small leucine-rich proteoglycan decorin, known to interfere with cellular events of tumorigenesis mainly by blocking various receptor tyrosine kinases (RTK) such as EGFR, Met, IGF-IR, PDGFR and VEGFR2. In this study, we characterized cell signaling events evoked by decorin deficiency in two experimental models of hepatocarcinogenesis using thioacetamide or diethyl nitrosamine as carcinogens. Genetic ablation of decorin led to enhanced tumor occurrence as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and a concurrent elevation in retinoblastoma protein phosphorylation via cyclin dependent kinase 4. Decreased steady state p21Waf1/Cip1 levels correlated with enhanced expression of transcription factor AP4, a known transcriptional repressor of p21Waf1/Cip1, and enhanced c-Myc protein levels. In addition, translocation of β-catenin was a typical event in diethyl nitrosamine-evoked tumors. In parallel, decreased phosphorylation of both c-Myc and β-catenin was observed in Dcn−/− livers likely due to the hindered GSK3β-mediated targeting of these proteins to proteasomal degradation. We discovered that in a genetic background lacking decorin, four RTKs were constitutively activated (phosphorylated), including three known targets of decorin such as PDGFRα, EGFR, IGF-IR, and a novel RTK MSPR/RON. Our findings provide powerful genetic evidence for a crucial in vivo role of decorin during hepatocarcinogenesis as lack of decorin in the liver and hepatic stroma facilitates experimental carcinogenesis by providing an environment devoid of this potent pan-RTK inhibitor. Thus, our results support future utilization of decorin as an antitumor agent in liver cancer.

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Section: Introductionmentioning

confidence: 99%

Decorin deficiency promotes hepatic carcinogenesis

et al. 2014

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“…Decorin and biglycan are members of the small leucine-rich proteoglycan (SLRP) gene family (Iozzo, 1999; Iozzo, 2011; Iozzo and Murdoch, 1996) that are involved in a number of biological processes including cancer growth (Iozzo and Cohen, 1993; Reed et al, 2005; Sofeu Feugaing et al, 2013), collagen fibrillogenesis and mechanical properties of connective tissues (Chen et al, 2011; Reed and Iozzo, 2002; Zhang et al, 2009), myogenesis (Brandan and Gutierrez, 2013), osteoarthritis and osteoporosis (Ameye et al, 2002; Ameye and Young, 2002; Nikitovic et al, 2012), stem cell biology (Berendsen et al, 2011; Bi et al, 2005; Ichii et al, 2012), immunity (Babelova et al, 2009; Merline et al, 2011; Moreth et al, 2012), and tumor angiogenesis and fibrosis (Neill et al, 2013; Neill et al, 2012a; Neill et al, 2012b). …”

Section: Introductionmentioning

confidence: 99%

Biglycan and decorin differentially regulate signaling in the fetal membranes

Horgan

Carr

et al. 2014

Matrix Biology

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Preterm birth is the leading cause of newborn mortality in the United States and about one third of cases are caused by preterm premature rupture of fetal membranes, a complication that is frequently observed in patients with Ehlers-Danlos Syndrome. Notably, a subtype of Ehlers-Danlos Syndrome is caused by expression of abnormal biglycan and decorin proteoglycans. As compound deficiency of these two small leucine-rich proteoglycans is a model of preterm birth, we investigated the fetal membranes of Bgn−/−;Dcn−/− double-null and single-null mice. Our results showed that biglycan signaling supported fetal membrane remodeling during early gestation in the absence of concomitant changes in TGFβ levels. In late gestation, biglycan signaling acted in a TGFβ–dependent manner to aid in membrane stabilization. In contrast, decorin signaling supported fetal membrane remodeling at early stages of gestation in a TGFβ–dependent manner, and fetal membrane stabilization at later stages of gestation without changes in TGFβ levels. Furthermore, exogenous soluble decorin was capable of rescuing the TGFβ signaling pathway in fetal membrane mesenchymal cells. Collectively, these findings provide novel targets for manipulation of fetal membrane extracellular matrix stability and could represent novel targets for research on preventive strategies for preterm premature rupture of fetal membranes.

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“…Decorin transduction reduced both the number and the size of colonies. Thus, decorin transduction alters the behavior of human colon cancer cells in vitro, further suggesting that decorin transduction could decrease cancer progression Sainio et al 2013;Santra et al 1995;Sofeu Feugaing et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The study also indicated that, although the disruption of the decorin gene did not lead to the spontaneous development of tumors, the lack of decorin was permissive for tumorigenesis (Bi et al 2008;Iozzo et al 1999). Thereafter, a great number of studies have focused on the antitumorigenic role of decorin in cancers (Goldoni and Iozzo 2008;Horvath et al 2014;Ma et al 2014;Moscatello et al 1998;Sainio et al 2013;Sainio and Järveläinen 2014;Sofeu Feugaing et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, decorin has recently been shown to contribute to autophagy of endothelial cells via paternally expressed gene 3 (Peg3) in response to vascular endothelial growth factor receptor 2 (VEGFR2)-mediated activation of AMP-activated protein kinase (AMPK) (Buraschi et al 2013;Goyal et al 2014). Consequently, it is not surprising that decorin is centrally involved in several physiological and pathological processes, including tumorigenesis (Bi et al 2012;Horváth et al 2014;Iozzo and Schaefer 2010;Shi et al 2014;Sofeu Feugaing et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Decorin in Human Colon Cancer

Nyman

Sainio

Pennanen

et al. 2015

J Histochem Cytochem.

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SummaryDecorin is generally recognized as a tumor suppressing molecule. Nevertheless, although decorin has been shown to be differentially expressed in malignant tissues, it has often remained unclear whether, in addition to non-malignant stromal cells, cancer cells also express it. Here, we first used two publicly available databases to analyze the current information about decorin expression and immunoreactivity in normal and malignant human colorectal tissue samples. The analyses demonstrated that decorin expression and immunoreactivity may vary in cancer cells of human colorectal tissues. Therefore, we next examined decorin expression in normal, premalignant and malignant human colorectal tissues in more detail using both in situ hybridization and immunohistochemistry for decorin. Our results invariably demonstrate that malignant cells within human colorectal cancer tissues are devoid of both decorin mRNA and immunoreactivity. Identical results were obtained for cells of neuroendocrine tumors of human colon. Using RT-qPCR, we showed that human colon cancer cell lines are also decorin negative, in accordance with the above in vivo results. Finally, we demonstrate that decorin transduction of human colon cancer cell lines causes a significant reduction in their colony forming capability. Thus, strategies to develop decorin-based adjuvant therapies for human colorectal malignancies are highly rational. (J Histochem Cytochem 63:710-720, 2015)

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More than matrix: The multifaceted role of decorin in cancer

Cited by 98 publications

References 129 publications

Decorin deficiency promotes hepatic carcinogenesis

Decorin deficiency promotes hepatic carcinogenesis

Biglycan and decorin differentially regulate signaling in the fetal membranes

Decorin in Human Colon Cancer

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