Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma

Zaghloul, Randa A.; El‐Shishtawy, Mamdouh M.; Galil, Khaled H. Abd El; Ebrahim, Mohamed A.; Metwaly, AbdelHamid A.; Al‐Gayyar, Mohammed M.H.

doi:10.1016/j.ejphar.2014.11.008

Cited by 17 publications

(10 citation statements)

References 47 publications

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“…Anti-GPC3 therapy was found to dowregulate insulin-like growth factor-II expression and downstream signaling involving downregulation of HSPGs, deactivation of sulfase-2 as well as a decrease of caspase-3 gene expression. This was strongly correlated to attenuation of HCC progression ( 46 ).…”

Section: Pgs Regulate Cytokine Signaling In Cancer Tissuesmentioning

confidence: 99%

Proteoglycans—Biomarkers and Targets in Cancer Therapy

et al. 2018

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Proteoglycans (PGs), important constituents of the extracellular matrix, have been associated with cancer pathogenesis. Their unique structure consisting of a protein core and glycosaminoglycan chains endowed with fine modifications constitutes these molecules as capable cellular effectors important for homeostasis and contributing to disease progression. Indeed, differential expression of PGs and their interacting proteins has been characterized as specific for disease evolvement in various cancer types. Importantly, PGs to a large extent regulate the bioavailability of hormones, growth factors, and cytokines as well as the activation of their respective receptors which regulate phenotypic diversibility, gene expression and rates of recurrence in specific tumor types. Defining and targeting these effectors on an individual patient basis offers ground for the development of newer therapeutic approaches which may act as either supportive or a substitute treatment to the standard therapy protocols. This review discusses the roles of PGs in cancer progression, developing technologies utilized for the defining of the PG “signature” in disease, and how this may facilitate the generation of tailor-made cancer strategies.

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Section: Pgs Regulate Cytokine Signaling In Cancer Tissuesmentioning

confidence: 99%

Proteoglycans—Biomarkers and Targets in Cancer Therapy

et al. 2018

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“…Sulfatase‐2 is an oncogenic that promotes the proliferation and migration of tumor cells. Sulfatase‐2 is known to degrade HSPGs reducing its anticancer activity with release of glypican‐3, cytokines and growth factor leading to enhancement of pathogenicity of tumor cells . HSPGs are a cell surface and extracellular matrix component.…”

Section: Discussionmentioning

confidence: 99%

“…Attack of HSPGs by sulfatase‐2 enhances the release of glypican‐3, growth factors and cytokines, which subsequently promote the malignant behaviour of the cancer cells . In addition, the interaction between sulfatase‐2 and glypican‐3 enhances the invasion and metastasis behaviour of tumor cells . However, no previous study illustrated the role of sulfatase‐2 in the pathogenicity of skin cancer.…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase‐2

Alyoussef

Taha

2018

Experimental Dermatology

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Although there are many treatment options for skin cancer, the chemotherapeutic agents for skin cancer are linked with many adverse effects as well as the development of multidrug resistance. Sulforaphane is an isothiocyanate, which is found in cruciferous vegetables. Consumption of sulforaphane‐rich diet has been linked to inhibition of UV‐exposed skin carcinogenesis. Therefore, the goal of this study was to determine the ability of sulforaphane to reduce skin cancer in mice through inhibition of sulfatase‐2 enzyme. Epicutaneous application of 7,12‐dimethylbenz (a) anthracene was performed on the shaved dorsal skin of mice followed by croton oil. Sulforaphane (9 μmol/mouse/day) was administered to mice orally. Skin was removed from the dorsal area for assessment of sulfatase‐2, glypican‐3, heparan sulphate proteoglycans (HSPGs), nuclear factor (NF)κB, nuclear factor E2‐related factor 2 (Nrf2), tumor necrosis factor (TNF)‐α, IL‐1β and caspase‐3. In addition, skin sections were stained with haematoxylin/eosin, Mallory and cytokeratin immunostaining. We found that, sulforaphane blocked sulfatase‐2 activity, leading to significant elevation in HSPGs as well as significant reduction in glypican‐3. In addition, sulforaphane significantly activated Nrf2 and reduced both the gene and protein expression of NFκB, TNF‐α, IL‐1β and caspase‐3. In parallel, stained sections obtained from skin cancer mice treated with sulforaphane showed significant reduction in hyperkeratosis, acanthosis and epithelial dysplasia. The collective results indicate that sulforaphane suppresses skin cancer via blocking sulfatase‐2 with subsequent elevation in HSPGs and reduction in glypican‐3. Moreover, sulforaphane attenuated skin cancer‐induced activation of inflammatory and apoptotic pathways.

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“…Upregulation of sulfatase-2 is considered oncogenic, and is associated with HCC in human, animal and tissue culture models (33,34). Sulfatase-2 enhances the expression of growth factors available to cell surface receptors, thus promoting the proliferation and migration of tumor cells.…”

Section: Enzymes Hydrolyzing Hspgsmentioning

confidence: 99%

Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma (Review)

Alshehri

Albalawi

et al. 2021

Oncol Lett

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Hepatocellular carcinoma (HCC) is one of the most common types of primary liver cancer. Despite advancements in the treatment strategies of HCC, there is an urgent requirement to identify and develop novel therapeutic drugs that do not lead to resistance. These novel agents should have the potential to influence the primary mechanisms participating in the pathogenesis of HCC. Heparan sulfate proteoglycans (HSPGs) are major elements of the extracellular matrix that perform structural and signaling functions. HSPGs protect against invasion of tumor cells by preventing cell infiltration and intercellular adhesion. Several enzymes, such as heparanase, matrix metalloproteinase-9 and sulfatase-2, have been reported to affect HSPGs, leading to their degradation and thus enhancing tumor invasion. In addition, some compounds that are produced from the degradation of HSPGs, including glypican-3 and syndecan-1, enhance tumor progression. Thus, the identification of enzymes that affect HSPGs or their degradation products in HCC may lead to the development of novel therapeutic targets. The present review discusses the main enzymes and compounds associated with HSPGs, and their involvement with the pathogenicity of HCC.

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Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma

Cited by 17 publications

References 47 publications

Proteoglycans—Biomarkers and Targets in Cancer Therapy

Proteoglycans—Biomarkers and Targets in Cancer Therapy

Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase‐2

Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma (Review)

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