Evidence map›Paper›PMID 39018437›Full record

ArticleThe British journal of dermatology2024

Chondroitin sulfate proteoglycan 4 increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying transforming growth factor-β signalling.

Allison R K Macaulay, Jianbo Yang, Matthew A Price, Colleen L Forster, Megan J Riddle, Christen L Ebens, Frank W Albert, Alessio Giubellino, James B McCarthy, Jakub Tolar

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The British journal of dermatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Allison R K MacaulayDivision of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, MN,USA.
Jianbo YangThe Cancer Center, Union Hospital, Fujian Medical University, Fuzhou, China.
Matthew A PriceMasonic Cancer Center, University of Minnesota, MN, USA.
Colleen L ForsterBiorepository and Laboratory Services, Clinical and Translational Science Institute, University of Minnesota, MN, USA.
Megan J RiddleDivision of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, MN,USA.
Christen L EbensDivision of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, MN,USA.
Frank W AlbertDepartment of Genetics, Cell Biology, and Genetics, University of Minnesota, MN, USA.
Alessio GiubellinoMasonic Cancer Center, University of Minnesota, MN, USA.
James B McCarthyMasonic Cancer Center, University of Minnesota, MN, USA.
Jakub TolarDivision of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota, MN,USA.

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Institutional Career Development CoreKL2TR002492 · NCATS · UNIVERSITY OF MINNESOTA · PI INGBAR, DAVID H · 2018 to 2022
$6.3M
Skin-targeted Cell Therapy for Recessive Dystrophic Epidermolysis BullosaR01AR063070 · NIAMS · UNIVERSITY OF MINNESOTA · PI Mark J Osborn, Jakub Tolar · 2013 to 2026
$4.5M
Elsa Pardee FoundationNCATS NIH HHS KL2 TR002492NCATS NIH HHS UL1 TR002494NCATS NIH HHS UL1TR002494NIAMS NIH HHS R01 AR063070NIH HHS NHLBI R01 AR063070
6 · The paper itself

Abstract

backgroundRecessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin-blistering disorder that often progresses to metastatic cutaneous squamous cell carcinoma (cSCC) at chronic wound sites. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell-surface proteoglycan that is an oncoantigen in multiple malignancies, where it modulates oncogenic signalling, drives epithelial-to-mesenchymal transition (EMT) and enables cell motility.

objectivesTo evaluate CSPG4 expression and function in RDEB cSCC.

methodsRDEB cSCC cell lines were used to assess CSPG4-dependent changes in invasive potential, transforming growth factor (TGF)-β1-stimulated signal activation and clinically relevant cytopathology metrics in an in vitro full-thickness tumour model. CSPG4 expression in RDEB cSCC and non-RDEB cSCC tumours was analysed via immunohistochemistry and single-cell RNA sequencing (scRNA-Seq), respectively.

resultsInhibiting CSPG4 expression reduced invasive potential in multiple RDEB cSCC cell lines and altered membrane-proximal TGF-β signal activation via changes in SMAD3 phosphorylation. CSPG4 expression was uniformly localized to basal layer keratinocytes in fibrotic RDEB skin and tumour cells at the tumour-stroma interface at the invasive front in RDEB cSCC tumours in vivo. Analysis of published scRNA-Seq data revealed that CSPG4 expression was correlated with an enhanced EMT transcriptomic signature in cells at the tumour-stroma interface of non-RDEB cSCC tumours. Cytopathological metrics, for example nucleus : cell area ratio, were influenced by CSPG4 expression in in vitro tumour models.

conclusionsWe determined that CSPG4 expression in RDEB cSCC cell lines enhanced the invasive potential of tumours. Mechanistically, CSPG4 was found to enhance membrane-proximal TGF-β-stimulated signalling via SMAD3, which is a key mediator of EMT in RDEB cSCC. The implication of these studies is that CSPG4 may represent a therapeutic target that can be leveraged for the clinical management of patients with RDEB cSCC.

Indexed as

Carcinoma, Squamous CellChondroitin Sulfate ProteoglycansEpidermolysis Bullosa DystrophicaNeoplasm InvasivenessSignal TransductionSkin NeoplasmsCell Line, TumorCell MovementChondroitin Sulfate Proteoglycan 4Epithelial-Mesenchymal TransitionHumansKeratinocytesMembrane ProteinsSmad3 ProteinTransforming Growth Factor betaTransforming Growth Factor beta1Chondroitin Sulfate Proteoglycan 4Chondroitin Sulfate ProteoglycansCSPG4 protein, humanMembrane ProteinsSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor betaTransforming Growth Factor beta1

Identifiers

PMID39018437
PMCPMC11663483

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.