{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:12:49Z","timestamp":1782817969108,"version":"3.54.5"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NHLBI R01 AR063070"],"award-info":[{"award-number":["NHLBI R01 AR063070"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR002492"],"award-info":[{"award-number":["KL2TR002492"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001287","name":"Elsa Pardee Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001287","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recessive 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate CSPG4 expression and function in RDEB cSCC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>RDEB cSCC cell lines were used to assess CSPG4-dependent changes in invasive potential, transforming growth factor (TGF)-\u03b21-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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Inhibiting CSPG4 expression reduced invasive potential in multiple RDEB cSCC cell lines and altered membrane-proximal TGF-\u03b2 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\u2013stroma 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\u2013stroma interface of non-RDEB cSCC tumours. Cytopathological metrics, for example nucleus : cell area ratio, were influenced by CSPG4 expression in in vitro tumour models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We determined that CSPG4 expression in RDEB cSCC cell lines enhanced the invasive potential of tumours. Mechanistically, CSPG4 was found to enhance membrane-proximal TGF-\u03b2-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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae295","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T18:40:03Z","timestamp":1721241603000},"page":"104-117","source":"Crossref","is-referenced-by-count":7,"title":["Chondroitin sulfate proteoglycan 4 increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying transforming growth factor-\u03b2 signalling"],"prefix":"10.1093","volume":"192","author":[{"given":"Allison R K","family":"Macaulay","sequence":"first","affiliation":[{"name":"Division of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota , MN ,","place":["USA"]},{"name":"Department of Genetics, Cell Biology, and Genetics, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Yang","sequence":"additional","affiliation":[{"name":"The Cancer Center, Union Hospital, Fujian Medical University , Fuzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Price","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , MN ,","place":["USA"]},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen L","family":"Forster","sequence":"additional","affiliation":[{"name":"Biorepository and Laboratory Services, Clinical and Translational Science Institute, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J","family":"Riddle","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christen L","family":"Ebens","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology, and Genetics, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Giubellino","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , MN ,","place":["USA"]},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , MN ,","place":["USA"]},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Tolar","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplant and Cellular Therapy, Department of Pediatrics, Medical School, University of Minnesota , MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"2024122223525673200_ljae295-B1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/bjd.18921","article-title":"Consensus reclassification of inherited 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