Inhibition of the signaling pathway of syndecan-1 by synstatin: A promising anti-integrin inhibitor of angiogenesis and proliferation in HCC in rats

Metwaly, Heba A.; El-Gayar, Amal M.; El‐Shishtawy, Mamdouh M.

doi:10.1016/j.abb.2018.06.007

Cited by 19 publications

(13 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thioacetamide metabolism produces a hepatotoxin metabolite that triggers the overproduction of reactive oxygen species (ROS), leading to liver fibrosis and cirrhosis, and ending with HCC 51 , 52 . This metabolite is produced by cytochrome2E1 (CYP2E1) 53 , the principal P450 for the metabolism of many xenobiotics, such as TAA 54 – 61 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

RETRACTED ARTICLE: Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway

Younis

Ghanim

Elmorsy

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

“…GSH usually counteracts the deleterious effects of oxidative stress. GSH also detoxifies many toxic compounds 52 . Our study found that concomitant and late treatment with 100 mg/kg taurine significantly conserved hepatocyte integrity, as indicated by the reduced serum activities of ALT, AST, and hepatic MDA.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway

Younis

Ghanim

Elmorsy

et al. 2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…The HS mimetics OTR4120 and OTR4131 exhibit anti-tumoral effects in human hepatocellular carcinoma by interfering with HSPGs-mediated RANTES signaling [253]. Synstatin, a short peptide mimicking the SDC1 ectodomain responsible for αvβ3 or αvβ5 integrin/IGF1 complex formation and receptor activation, has been proved to be effective in mammary tumors and hepatocellular carcinoma [210,226,254]. Another approach in cancer therapy uses HS mimetics in conjunction with inhibitors of the exosites of proteases (i.e., cathepsins), thus interfering with HS/proteinase binding and proteinase catalytic activities [254].…”

Section: Heparan Sulfate Proteoglycans As Therapeutic Targets For Cancermentioning

confidence: 99%

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Pasquale

Pavone

2020

IJMS

View full text Add to dashboard Cite

In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.

show abstract

“…Clinically, a selective peptide inhibitor of the syndecan-1-IGF-1R-αvβ3 integrin complex, synstatin, was developed to competitively displace IGF-1R and integrin from syndecan and inactivate the complex [ 27 , 28 ]. A preclinical study of synstatin using a rat HCC model showed that inhibiting HCC in vivo by downregulating the integrin αvβ3 receptor reduced activation of the angiogenic growth factors, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF/FGF-2) [ 29 ], suggesting that this could be a promising targeted therapy in HCC.…”

Section: Cell Surface Proteoglycan (Transmembrane): Syndecan-1/cd1mentioning

confidence: 99%

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Tanaka

Tateishi

Koike

2018

IJMS

View full text Add to dashboard Cite

Proteoglycans, which consist of a protein core and glycosaminoglycan chains, are major components of the extracellular matrix and play physiological roles in maintaining tissue homeostasis. In the carcinogenic tissue microenvironment, proteoglycan expression changes dramatically. Altered proteoglycan expression on tumor and stromal cells affects cancer cell signaling pathways, which alters growth, migration, and angiogenesis and could facilitate tumorigenesis. This dysregulation of proteoglycans has been implicated in the pathogenesis of diseases such as hepatocellular carcinoma (HCC) and the underlying mechanism has been studied extensively. This review summarizes the current knowledge of the roles of proteoglycans in the genesis and progression of HCC. It focuses on well-investigated proteoglycans such as serglycin, syndecan-1, glypican 3, agrin, collagen XVIII/endostatin, versican, and decorin, with particular emphasis on the potential of these factors as biomarkers and therapeutic targets in HCC regarding the future perspective of precision medicine toward the “cure of HCC”.

show abstract

Inhibition of the signaling pathway of syndecan-1 by synstatin: A promising anti-integrin inhibitor of angiogenesis and proliferation in HCC in rats

Cited by 19 publications

References 65 publications

RETRACTED ARTICLE: Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway

RETRACTED ARTICLE: Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Contact Info

Product

Resources

About