The matricellular functions of small leucine-rich proteoglycans (SLRPs)

Merline, Rosetta; Schaefer, Roland M.; Schaefer, Liliana

doi:10.1007/s12079-009-0066-2

Cited by 159 publications

(174 citation statements)

References 150 publications

(266 reference statements)

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“…Thus, we hypothesized that aberrant expression of proteoglycans is a more frequent event and plays many physiological and pathological roles in the development and progression of tumors and merits further investigation. It is clear that SLRPs are biologically active components of ECM (26). ASPN, a new member of the SLRPs, is expressed abundantly in several malignant tumors, suggesting its involvement in the tumorigenesis and progression of cancer (6).…”

Section: Discussionmentioning

confidence: 99%

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

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Abstract. Asporin (ASPN), a novel member of the small leucine-rich proteoglycan (SLRP) family, serves as a key component of the tumor stroma and has been reported to be abnormally expressed in certain types of tumors. Specifically, the proteoglycan was proven to activate the coordinated invasion of scirrhous gastric cancer and cancer-associated fibroblasts. However, the role of ASPN in cancer cell growth and metastasis has not yet been addressed. In the present study, we aimed to evaluate the tumoricidal benefits of ASPN on tumorigenesis and progression of gastric cancer. Firstly, it was demonstrated that ASPN was overexpressed in gastric carcinoma tissues when compared to the corresponding non-cancerous tissues, and it had varied levels of expression in gastric cancer epithelial cell lines. Additionally, we assessed the effects of transient siRNA-mediated ASPN knockdown on gastric cancer cells. ASPN silencing inhibited proliferation and suppressed the migration of immortalized neoplastic epithelial cells. Furthermore, at the molecular level, we found that downregulation of ASPN blocked the anti-apoptotic molecule Bcl-2, increased the expression of pro-apoptotic molecule Bad, reduced the expression of migration-related proteins CD44 and matrix metalloproteinase (MMP)-2, and abrogated the activation of the phosphorylation status of ERK and epidermal growth factor (EGF) and its receptor (EGFR). Collectively, our findings indicate that ASPN is upregulated and plays an oncogenic role in gastric cancer progression and metastasis by influencing the EGFR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

2015

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“…The role of Bgn in regulating cellular proliferation was addressed only in a limited number of studies (36). Recent studies using cDNA and proteomic technologies demonstrated a down-regulated mRNA expression of Bgn and decorin in osteosarcoma, leukemia, intrahepatic cholangiocarcinoma, and melanoma (21)(22)(23)37).…”

Section: Discussionmentioning

confidence: 99%

HER-2/neu-mediated Down-regulation of Biglycan Associated with Altered Growth Properties

Recktenwald

Leisz

Steven

et al. 2012

Journal of Biological Chemistry

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“…117 However, they are now recognized as key signaling molecules, mediating cell-matrix crosstalk and regulating cell behavior, suggesting their biological activity extends far beyond the ability to bind collagens. 118,119 Several SLRPs show altered expression levels during pressure overload-induced remodeling, 120, 121 but there is limited knowledge about their roles in the failing heart.…”

Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

et al. 2013

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Sustained pressure overload induces heart failure, the main cause of mortality in the Western world. Increased understanding of the underlying molecular mechanisms is essential to improve heart failure treatment. Despite important functions in other tissues, cardiac proteoglycans have received little attention. Syndecan‐4, a transmembrane heparan sulfate proteoglycan, is essential for pathological remodeling, and we here investigated its expression and shedding during heart failure. Pressure overload induced by aortic banding for 24 h and 1 week in mice increased syndecan‐4 mRNA, which correlated with mRNA of inflammatory cytokines. In cardiac myocytes and fibroblasts, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide through the toll‐like receptor‐4, induced syndecan‐4 mRNA. Bioinformatical and mutational analyses in HEK293 cells identified a functional site for the proinflammatory nuclear factor‐κB transcription factor in the syndecan‐4 promoter, and nuclear factor‐κB regulated syndecan‐4 mRNA in cardiac cells. Interestingly, tumor necrosis factor‐α, interleukin‐1β and lipopolysaccharide induced nuclear factor‐κB‐dependent shedding of the syndecan‐4 ectodomain from cardiac cells. Overexpression of syndecan‐4 with mutated enzyme‐interacting domains suggested enzyme‐dependent heparan sulfate chains to regulate shedding. In cardiac fibroblasts, lipopolysaccharide reduced focal adhesion assembly, shown by immunohistochemistry, suggesting that inflammation‐induced shedding affects function. After aortic banding, a time‐dependent cardiac recruitment of T lymphocytes was observed by measuring CD3, CD4 and CD8 mRNA, which was reduced in syndecan‐4 knockout hearts. Finally, syndecan‐4 mRNA and shedding were upregulated in failing human hearts. Conclusively, our data suggest that syndecan‐4 plays an important role in the immune response of the heart to increased pressure, influencing cardiac remodeling and failure progression.

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The matricellular functions of small leucine-rich proteoglycans (SLRPs)

Abstract: The small leucine-rich proteoglycans (SLRPs) are biologically active components of the extracellular matrix (ECM

Cited by 159 publications

References 150 publications

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

HER-2/neu-mediated Down-regulation of Biglycan Associated with Altered Growth Properties

Innate immune signaling induces expression and shedding of the heparan sulfate proteoglycan syndecan‐4 in cardiac fibroblasts and myocytes, affecting inflammation in the pressure‐overloaded heart

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