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We here analysed the role of MIF and CD74 in the progression of hepatocellular carcinoma (HCC) in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Multilocular HCC was induced using the diethylnitrosamine\/carbon tetrachloride (DEN\/CCl<jats:sub>4<\/jats:sub>) model in hepatocyte\u2010specific <jats:italic>Mif<\/jats:italic> knockout (<jats:italic>Mif<\/jats:italic> <jats:sup>\u0394hep<\/jats:sup>), <jats:italic>Cd74<\/jats:italic>\u2010deficient, and control mice. Tumour burden was compared between the genotypes. MIF, CD74 and Ki67 expression were investigated in tumour and surrounding tissue. In vitro, the effects of the MIF\/CD74 axis on the proliferative and apoptotic behaviour of hepatoma cells and respective signalling pathways were assessed after treatment with MIF and anti\u2010CD74 antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>DEN\/CCl<jats:sub>4<\/jats:sub> treatment of <jats:italic>Mif<\/jats:italic> <jats:sup>\u0394hep<\/jats:sup> mice resulted in reduced tumour burden and diminished proliferation capacity within tumour tissue. In vitro<jats:italic>,<\/jats:italic> MIF stimulated proliferation of Hepa 1\u20136 and HepG2 cells, inhibited therapy\u2010induced cell death and induced ERK activation. The investigated effects could be reversed using a neutralizing anti\u2010CD74 antibody, and <jats:italic>Cd74<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice developed fewer tumours associated with decreased proliferation rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We identified a pro\u2010tumorigenic role of MIF during proliferation and therapy\u2010induced apoptosis of HCC cells. These effects were mediated via the MIF cognate receptor CD74. Thus, inhibition of the MIF\/CD74 axis could represent a promising target with regard to new pharmacological therapies aimed at HCC.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15622","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T05:56:10Z","timestamp":1626069370000},"page":"4452-4467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Macrophage migration inhibitory factor exerts pro\u2010proliferative and anti\u2010apoptotic effects via CD74 in murine hepatocellular carcinoma"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2778-2447","authenticated-orcid":false,"given":"Theresa H.","family":"Wirtz","sequence":"first","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Saal","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Heinrichs","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa F.","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Koenen","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Djudjaj","sequence":"additional","affiliation":[{"name":"Institute of Pathology RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai M.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Institute of Pathology RWTH Aachen University  Aachen Germany"},{"name":"Department of Nephrology and Immunology RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bucala","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC) University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Bernhagen","sequence":"additional","affiliation":[{"name":"Division of Vascular Biology, Institute for Stroke and Dementia Research (ISD) Ludwig Maximilian\u2010University (LMU) and LMU University Hospital  Munich Germany"},{"name":"Munich Cluster for Systems Neurology (EXC 2145 SyNergy)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Luise","family":"Berres","sequence":"additional","affiliation":[{"name":"Department of Medicine III University Hospital RWTH Aachen  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","first-page":"S1","article-title":"THE CONCISE GUIDE TO PHARMACOLOGY 2019\/20: Other protein targets","volume":"176","author":"Alexander S. 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