{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:16:52Z","timestamp":1760149012282,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,17]],"date-time":"2023-06-17T00:00:00Z","timestamp":1686960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["HA6145\/6-1","HA6145\/7-1"],"award-info":[{"award-number":["HA6145\/6-1","HA6145\/7-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the RHOA mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because RHOA is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration. Therefore, this study aimed to elucidate the impact of the RHOA variant G17V on the migration of neoplastic T cells. We transfected the T-cell lymphoma cell lines HH and HuT78 to stably express the RHOA-G17V variant. RHOA-G17V-expressing T cells did not exhibit enhanced motility compared to empty-vector-transfected cells in microchannels, a 3D collagen gel, or primary human lymphatic tissue. Cells of the HH cell line expressing RHOA-G17V had an increased number of cells with cleaved collagen compared with the empty-vector-transfected cells. Therefore, we hypothesized that the early spread of AITL tumor cells may be related to remodelling of the extracellular matrix. Accordingly, we observed a significant negative correlation between the relative area of collagen in histological sections from 18 primary AITL and the allele frequency of the RHOA-G17V mutation. In conclusion, our results suggest that the characteristic presentation of AITL with early, widespread dissemination of lymphoma cells is not the result of an enhanced migration capacity due to the RHOA-G17V mutation; instead, this feature may rather be related to extracellular matrix remodelling.<\/jats:p>","DOI":"10.3390\/cancers15123226","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:59:51Z","timestamp":1687139991000},"page":"3226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The RHOA Mutation G17V Does Not Lead to Increased Migration of Human Malignant T Cells but Is Associated with Matrix Remodelling"],"prefix":"10.3390","volume":"15","author":[{"given":"Katrin","family":"Merk-Ahmad","sequence":"first","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Bein","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-7027","authenticated-orcid":false,"given":"Sonja","family":"Scharf","sequence":"additional","affiliation":[{"name":"Frankfurt Institute for Advanced Studies, 60438 Frankfurt am Main, Germany"},{"name":"Molecular Bioinformatics, Goethe University Frankfurt am Main, Robert-Mayer-Str. 11-15, 60325 Frankfurt am Main, Germany"},{"name":"Institute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-250X","authenticated-orcid":false,"given":"Hendrik","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Frankfurt Institute for Advanced Studies, 60438 Frankfurt am Main, Germany"},{"name":"Institute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Bexte","sequence":"additional","affiliation":[{"name":"Department for Pediatrics, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Experimental Immunology and Cell Therapy, Department of Pediatrics, Goethe University, 60528 Frankfurt am Main, Germany"},{"name":"Frankfurt Cancer Institute, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"University Cancer Center (UCT) Frankfurt, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8530-1192","authenticated-orcid":false,"given":"Evelyn","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Department for Pediatrics, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Experimental Immunology and Cell Therapy, Department of Pediatrics, Goethe University, 60528 Frankfurt am Main, Germany"},{"name":"Frankfurt Cancer Institute, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"German Cancer Consortium (DKTK), Partner Site Frankfurt\/Mainz, 60528 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas G.","family":"Loth","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, University Hospital Frankfurt, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Flinner","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Senff","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, Helios Klinikum Wuppertal, 42283 Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Schneider","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin-Leo","family":"Hansmann","sequence":"additional","affiliation":[{"name":"Frankfurt Institute for Advanced Studies, 60438 Frankfurt am Main, Germany"},{"name":"Institute of General Pharmacology and Toxicology, Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Piel","sequence":"additional","affiliation":[{"name":"Institut Curie and Institut Pierre Gilles de Gennes, CNRS, UMR 144, PSL Research University, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"H\u00e4upl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 2, Goethe University Hospital, 60590 Frankfurt am Main, Germany"},{"name":"German Cancer Consortium, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Oellerich","sequence":"additional","affiliation":[{"name":"Frankfurt Cancer Institute, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"University Cancer Center (UCT) Frankfurt, University Hospital, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Department of Internal Medicine 2, Goethe University Hospital, 60590 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-7254","authenticated-orcid":false,"given":"Emmanuel","family":"Donnadieu","sequence":"additional","affiliation":[{"name":"Institut Cochin, INSERM U1016, CNRS UMR 8104, Universit\u00e9 Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e361","DOI":"10.3324\/haematol.2015.126300","article-title":"Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets","volume":"100","author":"Parrens","year":"2015","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1182\/blood.2022015851","article-title":"The International Consensus Classification of Mature Lymphoid Neoplasms: A report from the Clinical Advisory 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