Changes in heparan sulfate sulfotransferases and cell-surface heparan sulfate during SKM-1 cells granulocytic differentiation and A549 cells epithelial-mesenchymal transition

Zhao, Shancheng; Wang, Zhen

doi:10.1007/s10719-019-09903-0

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…[34] Acetyl HS, which has multiple sulfation patterns, is one of the important regulators of cancer cells by interacting with multiple growth factors, while HS2ST1 was found to be downregulated at both mRNA and protein levels during granulocyte differentiation in SKM-1 leukemia cells, and HS (glucosamine) 3-O sulfotransferase 3A (HS3ST3A) in epithelial-mesenchymal transition of A549 lung cancer cells, while cell surface HS recognized by anti-HS antibodies was also altered in both cancer cell lines. [35] This is consistent with our study. Our study suggests that HS2ST1 also presents as dysregulated in OS and its significant dysregulation may be a key factor contributing to the poor prognosis of OS.…”

Section: Discussionsupporting

confidence: 94%

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

et al. 2022

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Introduction: Prognostic biomarkers for osteosarcoma (OS) are still very few, and this study aims to examine 2 novel prognostic biomarkers for OS through combined bioinformatics and experimental approach.Materials and methods: Expression profile data of OS and paraneoplastic tissues were downloaded from several online databases, and prognostic genes were screened by differential expression analysis, Univariate Cox analysis, least absolute shrinkage and selection operator regression analysis, and multivariate Cox regression analysis to construct prognostic models. The accuracy of the model was validated using principal component analysis, constructing calibration plots, and column line plots. We also analyzed the relationship between genes and drug sensitivity. Gene expression profiles were analyzed by immunocytotyping. Also, protein expressions of the constructed biomarkers in OS and paraneoplastic tissues were verified by immunohistochemistry.Results: Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) and Syndecan 3 (SDC3, met all our requirements after screening. The constructed prognostic model indicated that patients in the high-risk group had a much lower patient survival rate than in the low-risk group. Moreover, these genes were closely related to immune cells (P < .05). Drug sensitivity analysis showed that the 2 genes modeled were strongly correlated with multiple drugs. Immunohistochemical analysis showed significantly higher protein expression of both genes in OS than in paraneoplastic tissues.Conclusions: HS2ST1 and SDC3 are significantly dysregulated in OS, and the prognostic models constructed based on these 2 genes have much lower survival rates in the high-risk group than in the low-risk group. HS2ST1 and SDC3 can be used as glycolytic and immune-related prognostic biomarkers in OS.

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Section: Discussionsupporting

confidence: 94%

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

et al. 2022

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“…Gene expression datasets from the Oncomine database were explored and revealed that 2OST1 expression is upregulated in prostate carcinoma and functional assays showed that it correlates with cell proliferation and invasion capabilities, known to enhance cancer cells metastatic behaviour (100). In the same line, but in a different model, it was demonstrated that downregulation of 2OST1, and concomitant change in HS structural patterns, accompanied the granulocytic differentiation of SKM-1 leukaemia cells and were associated with cells' growth inhibition and less aggressive phenotypes (101). In breast cancer, 2OST1 expression was shown to promote the acquisition of cancer stem cell-like properties, by activating stemness-associated signalling pathways (102).…”

Section: Sulfotransferase Deregulation and Aberrant Hs Sulfation Profilesmentioning

confidence: 95%

Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression

et al. 2021

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Heparan Sulfate Proteoglycans (HSPGs) are important cell surface and Extracellular Matrix (ECM) maestros involved in the orchestration of multiple cellular events in physiology and pathology. These glycoconjugates bind to various bioactive proteins via their Heparan Sulfate (HS) chains, but also through the protein backbone, and function as scaffolds for protein-protein interactions, modulating extracellular ligand gradients, cell signalling networks and cell-cell/cell-ECM interactions. The structural features of HS chains, including length and sulfation patterns, are crucial for the biological roles displayed by HSPGs, as these features determine HS chains binding affinities and selectivity. The large HS structural diversity results from a tightly controlled biosynthetic pathway that is differently regulated in different organs, stages of development and pathologies, including cancer. This review addresses the regulatory mechanisms underlying HS biosynthesis, with a particular focus on the catalytic activity of the enzymes responsible for HS glycan sequences and sulfation motifs, namely D-Glucuronyl C5-Epimerase, N- and O-Sulfotransferases. Moreover, we provide insights on the impact of different HS structural epitopes over HSPG-protein interactions and cell signalling, as well as on the effects of deregulated expression of HS modifying enzymes in the development and progression of cancer. Finally, we discuss the clinical potential of HS biosynthetic enzymes as novel targets for therapy, and highlight the importance of developing new HS-based tools for better patients’ stratification and cancer treatment.

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“…SKM-1 cells have not been a widely employed as a AML-MDS biological model in research. Nevertheless, the range of research areas in which they have been exploited includes induction of cell death [62,63], proliferation [64] and cell cycle [65,66], differentiation [67,68], gene expression [69] and its epigenetic regulation [70] or drug resistance [71], usually as a response to a particular substance [72] or nanoconjugates [73,74].…”

Section: Introductionmentioning

confidence: 99%

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates

et al. 2021

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Acute myeloid leukemia (AML) is a highly aggressive type of cancer caused by the uncontrolled proliferation of undifferentiated myeloblasts, affecting the bone marrow and blood. Systemic chemotherapy is considered the primary treatment strategy; unfortunately, healthy cells are also affected to a large extent, leading to severe side effects of this treatment. Targeted drug therapies are becoming increasingly popular in modern medicine, as they bypass normal tissues and cells. Two-dimensional MoS2-based nanomaterials have attracted attention in the biomedical field as promising agents for cancer diagnosis and therapy. Cancer cells typically (over)express distinctive cytoplasmic membrane-anchored or -spanning protein-based structures (e.g., receptors, enzymes) that distinguish them from healthy, non-cancerous cells. Targeting cancer cells via tumor-specific markers using MoS2-based nanocarriers loaded with labels or drugs can significantly improve specificity and reduce side effects of such treatment. SKM-1 is an established AML cell line that has been employed in various bio-research applications. However, to date, it has not been used as the subject of studies on selective cancer targeting by inorganic nanomaterials. Here, we demonstrate an efficient targeting of AML cells using MoS2 nanoflakes prepared by a facile exfoliation route and functionalized with anti-CD33 antibody that binds to CD33 receptors expressed by SKM-1 cells. Microscopic analyses by confocal laser scanning microscopy supplemented by label-free confocal Raman microscopy proved that (anti-CD33)-MoS2 conjugates were present on the cell surface and within SKM-1 cells, presumably having been internalized via CD33-mediated endocytosis. Furthermore, the cellular uptake of SKM-1 specific (anti-CD33)-MoS2 conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS2 conjugates. Our results indicate the importance of appropriate functionalization of MoS2 nanomaterials by tumor-recognizing elements that significantly increase their specificity and hence suggest the utilization of MoS2-based nanomaterials in the diagnosis and therapy of AML.

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Changes in heparan sulfate sulfotransferases and cell-surface heparan sulfate during SKM-1 cells granulocytic differentiation and A549 cells epithelial-mesenchymal transition

Cited by 9 publications

References 35 publications

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates

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Changes in heparan sulfate sulfotransferases and cell-surface heparan sulfate during SKM-1 cells granulocytic differentiation and A549 cells epithelial-mesenchymal transition

Cited by 9 publications

References 35 publications

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3

Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS2-based nanoconjugates

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Product

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Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS₂-based nanoconjugates