{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:28:33Z","timestamp":1784892513710,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is an increasing number of studies showing that thrombocytosis\u2014accompanying a variety of solid tumors including colorectal cancer (CRC)\u2014is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR\/cas9 IL-6 knockout (KO) strain. Adult male FB\/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)\/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET\/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions.<\/jats:p>","DOI":"10.3390\/ijms21176218","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T09:17:08Z","timestamp":1598606228000},"page":"6218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Thrombocytosis and Effects of IL-6 Knock-Out in a Colitis-Associated Cancer Model"],"prefix":"10.3390","volume":"21","author":[{"given":"Valeria","family":"Josa","sequence":"first","affiliation":[{"name":"Jahn Ferenc Del-pesti Korhaz es Rendelointezet, Department of Otorhinolaryngology and Head and Neck Surgery, 1135 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilamer","family":"Ferenczi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Szalai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniko","family":"Fuder","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uzsoki utcai Hospital, 1145 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kuti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Horvath","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolett","family":"Hegedus","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary"},{"name":"CROmed Translational Research Ltd., 1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-0397","authenticated-orcid":false,"given":"Tibor","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, University of Pannonia, Institute of Radiochemistry and Radioecology, 8200 Veszpr\u00e9m, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergo","family":"Bagamery","sequence":"additional","affiliation":[{"name":"Mediso Medical Imaging Systems Ltd., 1037 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Juhasz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Winkler","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9687-3556","authenticated-orcid":false,"given":"Daniel S.","family":"Veres","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsombor","family":"Zrubka","sequence":"additional","affiliation":[{"name":"University Research, Innovation and Service Center, University of \u00d3buda, 1034 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-0413","authenticated-orcid":false,"given":"Domokos","family":"Mathe","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, Hungary"},{"name":"CROmed Translational Research Ltd., 1094 Budapest, Hungary"},{"name":"Hungarian Center for Excellence in Molecular Medicine, 6723 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-0302","authenticated-orcid":false,"given":"Zsolt","family":"Baranyai","sequence":"additional","affiliation":[{"name":"1st Department of Surgery, Semmelweis University, 1082 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Global Burden of Disease Cancer Collaboration, Fitzmaurice, C., Akinyemiju, T.F., Al Lami, F.H., Alam, T., Alizadeh-Navaei, R., Allen, C., Alsharif, U., Alvis-Guzman, N., and Amini, E. 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