{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:54:07Z","timestamp":1793084047439,"version":"4.5.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We studied the biological features and the immunophenotype of a cell culture established from the lesion of soft tissues of a woman affected by Gorham-Stout syndrome. We found that these cells belonged to a monocytic lineage with some characteristics of immature osteoclasts and were able to release large amounts of osteoclastogenic and angiogenic molecules that may contribute to disease progression.<\/jats:p><jats:p>Introduction: Gorham-Stout syndrome is a rare disease characterized by osteolysis and proliferation of vascular or lymphatic vessels, with a severe outcome. Its etiology and the identification of the cell types involved are completely unknown.<\/jats:p><jats:p>Materials and Methods: A cell culture from a lesion of soft tissues was established, and its behavior in vitro and in immunodeficient mice was studied. We analyzed (1) the cell phenotype by flow cytometry; (2) the adhesive and migratory properties on different substrates; (3) the ability to differentiate into mature osteoclasts; (4) the production of osteclastogenic and angiogenic molecules; (5) the in vivo angiogenic activity of the cells subcutaneously implanted in mouse in a Matrigel plug; and (6) the ability to recapitulate the disease when transplanted in nude mice.<\/jats:p><jats:p>Results and Conclusions: The established culture consisted of a morphologically homogeneous cell population belonging to a monocytic lineage having some features of an osteoclast-like cell type. Cells had an invasive phenotype, were angiogenic, and produced osteoclastogenic (IL-6, TGF-\u03b21, IL-1\u03b2) and angiogenic (vascular endothelial growth factor-A {VEGF-A}, CXCL-8) molecules when challenged with inflammatory cytokines. Immunodeficient mice injected with these cells did not show any bone lesions or vascular alteration, but had high amounts of circulating human IL-6 and VEGF-A. Cells isolated from a cutaneous lymphangiomatosis did not show any of these findings. These data suggest that cells of monocyte-macrophage lineage play an essential role in the pathogenesis of Gorham-Stout disease, whose progression is propelled by cytokine circuits that accelerate angiogenesis and osteoclastogenesis.<\/jats:p>","DOI":"10.1359\/jbmr.051019","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T13:26:28Z","timestamp":1146057988000},"page":"207-218","source":"Crossref","is-referenced-by-count":67,"title":["Gorham-Stout Syndrome: A Monocyte-Mediated Cytokine Propelled Disease"],"prefix":"10.1093","volume":"21","author":[{"given":"Silvia","family":"Colucci","sequence":"first","affiliation":[{"name":"Istituto di Anatomia Umana Normale, Universit\u00e0 di Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Taraboletti","sequence":"additional","affiliation":[{"name":"Istituto per le Ricerche Farmacologiche \u201cNegri Bergamo,\u201d Bergamo, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Valdembri","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Oncologiche, Universit\u00e0 di Torino, Candiolo, Italy"},{"name":"Istituto per la Cura e la Ricerca sul Cancro, Universit\u00e0 di Torino, Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Geuna","sequence":"additional","affiliation":[{"name":"Istituto per la Cura e la Ricerca sul Cancro and Azienza Sanitaria Ospedaliera \u201cOrdine Mauriziano,\u201d Laboratorio di Immunologia dei Tumori, Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pagano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche e Oncologia, Universit\u00e0 di Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grano","sequence":"additional","affiliation":[{"name":"Istituto di Anatomia Umana Normale, Universit\u00e0 di Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M","family":"Pogrel","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian L","family":"Harris","sequence":"additional","affiliation":[{"name":"Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas N","family":"Athanasou","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oxford, Nuffield Orthopaedic Centre, Nuffield, United 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