{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T23:42:38Z","timestamp":1781566958825,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T00:00:00Z","timestamp":1572393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HA6145\/2-1, HE 3552\/4-2, HA 1284\/7-2, KU1315\/9-2"],"award-info":[{"award-number":["HA6145\/2-1, HE 3552\/4-2, HA 1284\/7-2, KU1315\/9-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterized by a proliferation of fibroblasts in the tumor microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancer-associated fibroblasts. However, to date a deep molecular characterization of these fibroblasts is lacking. Thus, the aim of the present study is a comprehensive characterization of these fibroblasts. Gene expression profiling and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic phenotype characterized by myocardin (MYOCD) expression. Moreover, TIMP3, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. As previously shown for other types of cancer-associated fibroblasts, treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin induced cell death. However, HRS cells adherent to fibroblasts were protected from Brentuximab-Vedotin induced injury. In summary, we confirm the importance of fibroblasts for HRS cell survival and identify TIMP3 which probably contributes as a major factor to the typical fibrosis observed in NS cHL.<\/jats:p>","DOI":"10.3390\/cancers11111687","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T05:18:26Z","timestamp":1572499106000},"page":"1687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Fibroblasts in Nodular Sclerosing Classical Hodgkin Lymphoma Are Defined by a Specific Phenotype and Protect Tumor Cells from Brentuximab-Vedotin Induced Injury"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4033-4966","authenticated-orcid":false,"given":"Katrin","family":"Bankov","sequence":"first","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Department of Internal Medicine 1, Hospital of the J.W. Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"D\u00f6ring","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-0029","authenticated-orcid":false,"given":"Adam","family":"Ustaszewski","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4760-8246","authenticated-orcid":false,"given":"Maciej","family":"Giefing","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Herling","sequence":"additional","affiliation":[{"name":"The Laboratory of Lymphocyte Signalling and Oncoproteome, Department I of Internal Medicine, Center for Integrated Oncology (CIO) Aachen-Bonn-Cologne-Duesseldorf, CECAD and CMMC, University of Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Cencioni","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Institute for Systems Analysis and Computer Science, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Spallotta","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Turin, 10060 Candiolo (Turin), Italy"},{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo (Turin), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Gaetano","sequence":"additional","affiliation":[{"name":"Laboratorio di Epigenetica, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-7191","authenticated-orcid":false,"given":"Ralf","family":"K\u00fcppers","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, 45122 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Reference and Consultant Center for Lymph Node and Lymphoma Pathology, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Frankfurt Institute of Advanced Studies, 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-1091","authenticated-orcid":false,"given":"Sylvia","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Reference and Consultant Center for Lymph Node and Lymphoma Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.pathol.4.110807.092209","article-title":"Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma","volume":"4","author":"Schmitz","year":"2009","journal-title":"Annu. 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