{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:15:47Z","timestamp":1792804547441,"version":"4.5.0"},"reference-count":186,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,26]],"date-time":"2018-04-26T00:00:00Z","timestamp":1524700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"People Programme (Marie Curie Actions) of the FP7-2013","award":["#PITN-GA-2012-316549"],"award-info":[{"award-number":["#PITN-GA-2012-316549"]}]},{"name":"Ministry of Economy, Industry and Competitiveness, Spain (cofounded by FEDER funds \/European Regional Development Fund - a way to build Europe)","award":["SAF2015-64149-R"],"award-info":[{"award-number":["SAF2015-64149-R"]}],"id":[{"id":"https:\/\/ror.org\/034900433","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ludwig Cancer Research Ltd, the Swedish Research Council","award":["K2013-66X-14936-10-5"],"award-info":[{"award-number":["K2013-66X-14936-10-5"]}],"id":[{"id":"https:\/\/ror.org\/03zttf063","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002794","name":"Swedish Cancer Society","doi-asserted-by":"publisher","award":["CAN 2015\/438"],"award-info":[{"award-number":["CAN 2015\/438"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Economy, Industry and Competitiveness, Spain","award":["BES-2016-0077564"],"award-info":[{"award-number":["BES-2016-0077564"]}],"id":[{"id":"https:\/\/ror.org\/034900433","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Instituto de Salud Carlos III, Spain","award":["CIBEREHD"],"award-info":[{"award-number":["CIBEREHD"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) is a cytokine essential for the induction of the fibrotic response and for the activation of the cancer stroma. Strong evidence suggests that a strong cross-talk exists among TGF-\u03b2 and the tissue extracellular matrix components. TGF-\u03b2 is stored in the matrix as part of a large latent complex bound to the latent TGF-\u03b2 binding protein (LTBP) and matrix binding of latent TGF-\u03b2 complexes, which is required for an adequate TGF-\u03b2 function. Once TGF-\u03b2 is activated, it regulates extracellular matrix remodelling and promotes a fibroblast to myofibroblast transition, which is essential in fibrotic processes. This cytokine also acts on other cell types present in the fibrotic and tumour microenvironment, such as epithelial, endothelial cells or macrophages and it contributes to the cancer-associated fibroblast (CAF) phenotype. Furthermore, TGF-\u03b2 exerts anti-tumour activity by inhibiting the host tumour immunosurveillance. Aim of this review is to update how TGF-\u03b2 and the tissue microenvironment cooperate to promote the pleiotropic actions that regulate cell responses of different cell types, essential for the development of fibrosis and tumour progression. We discuss recent evidences suggesting the use of TGF-\u03b2 chemical inhibitors as a new line of defence against fibrotic disorders or cancer.<\/jats:p>","DOI":"10.3390\/ijms19051294","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T06:52:23Z","timestamp":1524811943000},"page":"1294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":335,"title":["TGF-\u03b2 and the Tissue Microenvironment: Relevance in Fibrosis and Cancer"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8786-8763","authenticated-orcid":false,"given":"Laia","family":"Caja","sequence":"first","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Box 582, 75123 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Dituri","sequence":"additional","affiliation":[{"name":"National Institute of Gastroenterology, \u201cS. de Bellis\u201d Research Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Mancarella","sequence":"additional","affiliation":[{"name":"National Institute of Gastroenterology, \u201cS. de Bellis\u201d Research Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2602-5578","authenticated-orcid":false,"given":"Daniel","family":"Caballero-Diaz","sequence":"additional","affiliation":[{"name":"TGF-\u03b2 and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l\u2019Hospitalet, 199, 08908 Barcelona, Spain"},{"name":"Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9131-3827","authenticated-orcid":false,"given":"Aristidis","family":"Moustakas","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Box 582, 75123 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Giannelli","sequence":"additional","affiliation":[{"name":"National Institute of Gastroenterology, \u201cS. de Bellis\u201d Research Hospital, Castellana Grotte, 70013 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Fabregat","sequence":"additional","affiliation":[{"name":"TGF-\u03b2 and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), Gran Via de l\u2019Hospitalet, 199, 08908 Barcelona, Spain"},{"name":"Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Physiological Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, L\u2019Hospitalet, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nrd4592","article-title":"Dissecting fibrosis: Therapeutic insights from the small-molecule toolbox","volume":"14","author":"Nanthakumar","year":"2015","journal-title":"Nat. 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