Emerging Role of Syndecans in Extracellular Matrix Remodeling in Cancer

Jang, Bohee; Kim, Ayoung; Hwang, Ji-Sun; Song, Ho Kyung; Kim, Yunjeon; Oh, Eok Soo

doi:10.1369/0022155420930112

Cited by 18 publications

(9 citation statements)

References 83 publications

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“…Eph receptors and their ligands are essential to the development and function of neuromuscular junctions and regulate actin cytoskeletal dynamics 42 , 43 . Syndecans including SDC1 mediate cytoskeletal organisation and remodelling of the extracellular matrix in cancer 44 . LRP1 promotes phagocytic activity, facilitating clearance of apoptotic cells 45 required for return towards tissue homeostasis.…”

Section: Discussionmentioning

confidence: 99%

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Ng,

Borst,

Gacaferi

et al. 2024

Nat Commun

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Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.

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Section: Discussionmentioning

confidence: 99%

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Ng,

Borst,

Gacaferi

et al. 2024

Nat Commun

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“…Eph receptors and their ligands are essential to the development and function of neuromuscular junctions and regulate actin cytoskeletal dynamics( 40, 41 ). Syndecans including SDC1 mediate cytoskeletal organisation and remodelling of the extracellular matrix in cancer( 42 ). LRP1 promotes phagocytic activity, facilitating clearance of apoptotic cells( 43 ) required for return towards tissue homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis

Borst

Gacaferi

et al. 2023

Preprint

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Fibrotic conditions are a significant global disease burden. While some therapies delay disease progression, none reverse fibrosis. To gain insights into how fibrosis might resolve, we developed a comparative single cell atlas of frozen shoulder capsule tissue; a chronic inflammatory fibrotic human disease that resolves spontaneously. We identified both a population of pro-inflammatory MERTKlowCD48+ macrophages (Mφ) and a population of MERTK+LYVE1+MRC1+Mφ enriched for negative regulators of inflammation. Micro-cultures of patient-derived cells identified cell-matrix interactions between MERTK+Mφ and DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in the resolution of frozen shoulder. Cross-tissue analysis revealed a shared gene expression cassette between MERTK+Mφ in the shoulder capsule and a similar cell population enriched in synovial tissues from rheumatoid arthritis patients in disease remi ssion, supporting the concept that MERTK+Mφ provide a cellular basis for the resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identified MERTK+LYVE1+MRC1+Mφ and DKK3+ and POSTN+ fibroblast populations analogous to those identified in adult shoulder capsule, suggesting that the template to resolve fibrosis is established during development. Therapeutic enhancement of crosstalk between MerTK+Mφ and pro-resolving DKK3+ and POSTN+ fibroblasts could accelerate resolution of frozen shoulder and resolve persistent inflammatory fibrotic disease in other tissues.

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“…Previous and recent data suggest that two members of the family, syndecan-1 and -4 are related to signaling downstream to FN exposure [ 47 ]. Syndecan-4 is known to play a role in the formation of focal adhesions in co-operation with integrin α5β1 [ 48 , 49 , 50 ] while syndecan-1 was shown to activate integrins and regulate focal adhesion assembly and FN fibrillogenesis during corneal cell migration in the context of wound healing [ 51 ]. Consequently, we can speculate that syndecans may be implicated in cell signaling or be affected by FN in psoriasis, too, at least for syndecan-1 according to our data.…”

Section: Discussionmentioning

confidence: 99%

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

Koliakou

Μanthou

Koumentakou

et al. 2022

IJMS

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Syndecans act as independent co-receptors to exert biological activities and their altered function is associated with many pathophysiological conditions. Here, syndecan-1 and -4 were examined in lesional skin of patients with psoriasis. Immunohistochemical staining confirmed altered syndecan-1 distribution and revealed absence of syndecan-4 expression in the epidermis. Fibronectin (FN)—known to influence inflammation and keratinocyte hyperproliferation via α5β1 integrin in psoriasis—was also decreased. Syndecan-1 and -4 expression was analyzed in freshly isolated lesional psoriatic human keratinocytes (PHK) characterized based on their proliferation and differentiation properties. mRNA levels of syndecan-1 were similar between healthy and PHK, while syndecan-4 was significantly decreased. Cell growth and release of the pro-inflammatory Tumor Necrosis Factor-alpha (TNFα) were selectively and significantly induced in PHKs plated on FN. Results from co-culture of healthy keratinocytes and psoriatic fibroblasts led to the speculation that at least one factor released by fibroblasts down-regulate syndecan-1 expression in PHK plated on FN. To assay if biological treatments for psoriasis target keratinocyte proliferation, gelatin-based patches enriched with inteleukin (IL)-17α or TNFα blockers were prepared and tested using a full-thickness healthy epidermal model (Phenion®). Immunohistochemistry analysis showed that both blockers impacted the localisation of syndecan-1 within the refined epidermis. These results provide evidence that syndecans expression are modified in psoriasis, suggesting that they may represent markers of interest in this pathology.

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Emerging Role of Syndecans in Extracellular Matrix Remodeling in Cancer

Cited by 18 publications

References 83 publications

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis

Altered Distribution and Expression of Syndecan-1 and -4 as an Additional Hallmark in Psoriasis

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