Lumican regulates osteosarcoma cell adhesion by modulating TGFβ2 activity

Nikitovic, Dragana; Chalkiadaki, Georgia; Berdiaki, Aikaterini; Aggelidakis, John; Katonis, Pavlos; Karamanos, Nikos K.; Tzanakakis, George N.

doi:10.1016/j.biocel.2011.03.008

Cited by 72 publications

(75 citation statements)

References 38 publications

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“…Importantly, protein levels of lumican correlated positively with lung weight during pressure overload-induced remodeling, suggesting an association between lumican and development of congestive heart failure. 121 Consistent with this, we found that protein levels of glycosylated lumican 221 were increased only in mice that had undergone transition to congestive heart failure, characterized by increased lung weight and LAD. Also, in agreement, lumican levels were elevated in LVs of patients with end-stage heart failure.…”

Section: The Multiple Roles Of Syndecan-4 In Cardiac Remodelingsupporting

confidence: 78%

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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Section: The Multiple Roles Of Syndecan-4 In Cardiac Remodelingsupporting

confidence: 78%

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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“…TGF-b proteins localize in the ECM in association with small leucine-rich proteoglycans (SLRPs) such as decorin, biglycan, lumican, and keratocan. [47][48][49] These interactions can regulate the TGF-b biological activity. [48][49][50] In an earlier report, we found FGF-2 modulates the type of SLRP molecules secreted by keratocytes 30 and that difference is evidenced here in Figures 8 and 9.…”

mentioning

confidence: 99%

“…[47][48][49] These interactions can regulate the TGF-b biological activity. [48][49][50] In an earlier report, we found FGF-2 modulates the type of SLRP molecules secreted by keratocytes 30 and that difference is evidenced here in Figures 8 and 9. We speculate that the complex synergy between the FGF-2 and TGF-b3 observed here may not arise as a unique feature of differential signaling pathways by TGF-b isoforms, but rather from differential interactions of TGF-b3 with corneal SLRP proteoglycans compared to other TGF-b isoforms.…”

mentioning

confidence: 99%

Bioengineering Organized, Multilamellar Human Corneal Stromal Tissue by Growth Factor Supplementation on Highly Aligned Synthetic Substrates

Mann

et al. 2013

Tissue Engineering Part A

102

119

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“…In human osteosarcoma cell lines, it was demonstrated that lumican had a novel out-in signaling circuit that inhibited endogenous TGF-β2 activity, resulting in downstream effector modulation including pSmad 2, integrin β1 and pFAK to regulate osteosarcoma adhesion [28]. Another study of lumican showed its potential correlation with the differentiation and progression of osteosarcoma [29]. EEF2 is a component of the mRNA surveillance SURF complex and catalyzes the GTP-dependent ribosomal translocation step during translation elongation.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomics analysis of human osteosarcoma by 2D DIGE with MALDI-TOF/TOF MS

Wang

zhang

Yang

et al. 2016

Journal of Bone Oncology

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Osteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. However, controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel protein targets will be critical to identify the path toward improving outcomes for patients. We attempted to identify potential protein markers or therapy targets of osteosarcoma and give a glance at tumorigenesis of osteosarcoma. A sensitive and accurate method was employed in comparative proteomic analysis between benign tumor and osteosarcoma. Tumor tissues obtained by open biopsy before induction chemotherapy were investigated With 2D DIGE and MALDI-TOF/TOF MS, 22 differentially expressed proteins were identified after database searching, including 8 up-regulated and 14 down-regulated proteins. We also validated the expression levels of interesting proteins(have higher Ratios(tumor/normal)) by Western blotting assay. Annotating by bioinformatic tools, we found structural and signal transduction associated proteins were in large percentage among altered level proteins. In particular, some low abundant proteins involving translation and transcription, such as EEF2(Elongation Factor 2), LUM Lumican 23 kDa Protein) and GTF2A2(Transcription Initiation Factor Iia Gamma Chain.), were firstly reported by our study comparing to previous observations. Our findings suggest that these differential proteins may be potential biomarkers for diagnosis or molecules for understanding of osteosarcoma tumorigenesis, coming with biologic, preclinical, and clinical trial efforts being described to improve outcomes for patients.

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Lumican regulates osteosarcoma cell adhesion by modulating TGFβ2 activity

Cited by 72 publications

References 38 publications

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

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

Bioengineering Organized, Multilamellar Human Corneal Stromal Tissue by Growth Factor Supplementation on Highly Aligned Synthetic Substrates

Comparative proteomics analysis of human osteosarcoma by 2D DIGE with MALDI-TOF/TOF MS

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