Syndecan-3 in Inflammation and Angiogenesis

Arokiasamy, Samantha; Balderstone, Michaela J. M.; Rossi, Giulia De; Whiteford, James R.

doi:10.3389/fimmu.2019.03031

Cited by 30 publications

(28 citation statements)

References 64 publications

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“…Syndecan-4 (Sdc-4) expression was also higher than that of Sdc-3 in healthy tissues analyzed from the BioGPS database ( Supplementary Figure 1). This analysis also shown that the expression of Sdc-3 (Supplementary Figure 1A) on healthy tissue is confined to spinal cord and brain, as previously described (13,14), while the expression of Sdc-4 (Supplementary Figure 1B) is broader. In a similar fashion to healthy tissue, the expression of Sdc-4 was more homogeneous across the different malignant cell lines (Figure 1F), while the expression of Sdc-3 was mostly enriched in skin cutaneous melanoma (SKCM) cell lines ( Figure 1E), in contrast to its low expression in normal skin (Supplementary Figure 1A).…”

Section: Expression Of Sdc-3 and Sdc-4 Is Significantly Dysregulated supporting

confidence: 82%

“…Apart from cancer cells, endothelial cells and macrophages were identified as Sdc-3 expressing cell populations. Expression of Sdc-3 by endothelial cells has been previously reported ( 21 ) in the context of inflammatory disease ( 47 ) but its potential role on tumor angiogenesis is still largely unexplored ( 14 ). Importantly, Sdc-3 expression correlated with a macrophage gene signature in several cancer types.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Syndecan-3 is known to be mainly expressed in the brain and nervous tissue and plays a key role in cell adhesion and migration (13,14). However, its expression is not restricted to neuronal tissues, and recent studies point to important roles of Sdc-3 in inflammatory disease, regulation of energy balance, cancer, angiogenesis, and viral infections (12,(14)(15)(16)(17)(18)(19)(20)(21)(22). There is some evidence that Sdc-3 is expressed in the TME and several cancer cell lines, including bladder cancer (23), hepatocellular carcinoma (22,24), mammary carcinoma (25), ovarian cancer (19,20), pancreatic cancer (26), prostate carcinoma (27), renal cell carcinoma (12,28), and several glioma cell lines (29).…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment

et al. 2020

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The syndecan (Sdc) family is comprised of four members of cell surface molecules (Sdc-1 to 4) with different biological functions. Syndecan-3 (Sdc-3) is known to be mainly expressed in the brain and nervous tissue and plays a key role in development, cell adhesion, and migration. Recent studies point to important roles for Sdc-3 in inflammatory disease, but the patterns of expression and significance of Sdc-3 in cancer remains unexplored. Here we show that Sdc-3 expression is upregulated on several cancer types, especially in solid tumors that are known to be hypoxic. The Cancer Genome Atlas program (TCGA) data demonstrated that Sdc-3 expression in the tumor microenvironment positively correlates with a hypoxia gene signature. To confirm a potential cause-effect, we performed experiments with tumor cell lines showing increased expression upon in vitro exposure to 1% oxygen or dimethyloxalylglycine, an inhibitor of prolyl hydroxylases, indicating that Sdc-3 expression is promoted by hypoxia inducible factors (HIFs). HIF-1α was responsible for this upregulation as confirmed by CRISPR-engineered tumor cells. Using single-cell RNA sequencing data of melanoma patients, we show that Sdc-3 is expressed on tumor associated macrophages, cancer cells, and endothelial cells. Syndecan-3 expression positively correlated with a macrophage gene signature across several TCGA cancer types. In vitro experiments demonstrated that hypoxia (1% oxygen) or treatment with IFN-γ stimulate Sdc-3 expression on RAW-264.7 derived macrophages, linking Sdc-3 expression to a proinflammatory response. Syndecan-3 expression correlates with a better patient overall survival in hypoxic melanoma tumors.

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Section: Expression Of Sdc-3 and Sdc-4 Is Significantly Dysregulated supporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment

et al. 2020

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“…The binding of α2-3- and/or α2-6-linked sialic acids as cellular receptors recruited in the host cell entry processes was described in several viral families isolated from humans, including Adenoviridae , Picornaviridae , Reoviridae , Paramyxoviridae and Polyomaviridae [ 40 , 41 , 42 , 43 , 44 ]. In the context of the virus-host interaction, some viruses genera employ the sialic acid- and Siglec-based mechanisms that avoid or deactivates host defence after pathogen invasion and underlie in the pathogenesis of acquired immune deficiency syndrome (AIDS) [ 45 , 46 , 47 , 48 ].…”

Section: Sialic Acids In Covs Infectionsmentioning

confidence: 99%

Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

Wielgat

Rogowski

Godlewska

et al. 2020

Cells

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Coronaviruses (CoVs) are a diverse family of the enveloped human and animal viruses reported as causative agents for respiratory and intestinal infections. The high pathogenic potential of human CoVs, including SARS-CoV, MERS-CoV and SARS-CoV-2, is closely related to the invasion mechanisms underlying the attachment and entry of viral particles to the host cells. There is increasing evidence that sialylated compounds of cellular glycocalyx can serve as an important factor in the mechanism of CoVs infection. Additionally, the sialic acid-mediated cross-reactivity with the host immune lectins is known to exert the immune response of different intensity in selected pathological stages. Here, we focus on the last findings in the field of glycobiology in the context of the role of sialic acid in tissue tropism, viral entry kinetics and immune regulation in the CoVs infections.

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Exploring the potential role of palladin in modulating human CAF/ECM functional units

Dolskii,

Alcantara dos Santos,

Andrake

et al. 2024

Cytoskeleton

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Fibroblasts, crucial for maintaining tissue homeostasis, significantly shape the tumor microenvironment (TME). In pancreatic cancer, a highly aggressive malignancy, cancer‐associated fibroblast (CAF)/extracellular matrix (ECM) units dominate the TME, influencing tumor initiation, progression, and treatment responses. Palladin, an actin‐associated protein, is vital for fibroblast structural integrity and activation, playing a key role in CAF/ECM functionality. Palladin interacts with cytoskeletal proteins such as alpha‐actinin (α‐Act) and can therefore regulate other proteins like syndecans, modulating cytoskeletal features, cell adhesion, integrin recycling, and signaling. In this review, we propose that targeting the palladin/α‐Act/syndecan interaction network could modulate CAF/ECM units, potentially shifting the TME from a tumor‐promoting to a tumor‐suppressive state. In silico data and reported studies to suggest that stabilizing palladin‐α‐Act interactions, via excess palladin, influences syndecan functions; potentially modulating integrin endocytosis via syndecan engagement with protein kinase C alpha as opposed to syndecan binding to α‐Act. This mechanism can then affect the distribution of active α5β1‐integrin between the plasma membrane and known intracellular vesicular compartments, thereby influencing the tumor‐suppressive versus tumor‐promoting functions of CAF/ECM units. Understanding these interactions offers likely future therapeutic avenues for stroma normalization in pancreatic and other cancers, aiming to inhibit tumor progression and improve future treatment outcomes.

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Syndecan-3 in Inflammation and Angiogenesis

Cited by 30 publications

References 64 publications

Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment

Hypoxia Promotes Syndecan-3 Expression in the Tumor Microenvironment

Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

Exploring the potential role of palladin in modulating human CAF/ECM functional units

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