{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:49Z","timestamp":1784557249848,"version":"3.55.0"},"reference-count":31,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,6]]},"abstract":"\n Thyroid hormones are important for physiology and homeostasis. In addition to nuclear thyroid hormone receptors, the plasma membrane protein integrin \u03b1\n v<\/jats:sub>\n \u03b2\n 3<\/jats:sub>\n has been recognized as a receptor for both thyroxine (T\n 4<\/jats:sub>\n ) and triiodothyronine (T\n 3<\/jats:sub>\n ). Here, we studied whether thyroid hormone promotes growth of murine lung cancer via \u03b1\n v<\/jats:sub>\n \u03b2\n 3<\/jats:sub>\n in vivo<\/jats:italic>\n . Murine Lewis lung carcinoma cells (3LL), stably transfected with luciferase, were injected into mouse lungs. Tumor growth in untreated mice was compared to hypothyroid mice and hypothyroid mice treated with T\n 3<\/jats:sub>\n or T\n 4<\/jats:sub>\n with or without the \u03b1\n v<\/jats:sub>\n \u03b2\n 3<\/jats:sub>\n inhibitor 3,5,3\u2032,5\u2032-tetraiodothyroacetic acid (Tetrac). Tumor progression was determined by serial\n in vivo<\/jats:italic>\n imaging of bioluminescence emitted from the tumor. Tumor weight was recorded at the end of the experiment. Neoangiogenesis was determined by immunohistochemistry for CD31. Tumor growth was reduced in hypothyroidism and increased by T\n 4<\/jats:sub>\n treatment. Strikingly, only T\n 4<\/jats:sub>\n but not T\n 3<\/jats:sub>\n treatment promoted tumor growth. This T\n 4<\/jats:sub>\n effect was abrogated by the \u03b1\n v<\/jats:sub>\n \u03b2\n 3<\/jats:sub>\n inhibitor Tetrac. Tumor weight and neoangiogenesis were also significantly increased only in T\n 4<\/jats:sub>\n -treated mice. The T\n 4<\/jats:sub>\n effect on tumor weight and neoangiogenesis was abolished by Tetrac.\n In vitro<\/jats:italic>\n , T4 did not stimulate 3LL cell proliferation or signaling pathway activation. We conclude that T\n 4<\/jats:sub>\n promotes lung cancer growth in this orthotopic mouse model. The tumor-promoting effect is mediated via the plasma membrane integrin \u03b1\n v<\/jats:sub>\n \u03b2\n 3<\/jats:sub>\n and increased neoangiogenesis rather than direct stimulation of 3LL cells. These data suggest that such effects of levothyroxine may need to be considered in cancer patients on T\n 4<\/jats:sub>\n substitution.\n <\/jats:p>","DOI":"10.1530\/erc-18-0353","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T08:37:37Z","timestamp":1553071057000},"page":"565-574","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":25,"title":["Thyroxine promotes lung cancer growth in an orthotopic mouse model"],"prefix":"10.1530","volume":"26","author":[{"given":"S","family":"Latteyer","sequence":"first","affiliation":[{"name":"1Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Christoph","sequence":"additional","affiliation":[{"name":"2Clinic for Bone Marrow Transplants, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Theurer","sequence":"additional","affiliation":[{"name":"3Institute of Pathology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G S","family":"H\u00f6nes","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K W","family":"Schmid","sequence":"additional","affiliation":[{"name":"3Institute of Pathology, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Moeller","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology, Diabetes and Metabolism, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref01","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1210\/en.2005-0102","article-title":"Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis","volume":"146","year":"2005","journal-title":"Endocrinology"},{"key":"ref131","first-page":"25","article-title":"Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL\/6 mice","volume":"38","year":"1991","journal-title":"Tokushima Journal of Experimental Medicine"},{"key":"ref41","first-page":"1619","article-title":"Nanotetrac targets integrin 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Time for a more precise nomenclature","volume":"158","year":"2017","journal-title":"Endocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1158\/1535-7163.MCT-13-0040","article-title":"UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo","volume":"12","year":"2013","journal-title":"Molecular Cancer Therapeutics"},{"key":"ref81","first-page":"959057","article-title":"Combined QM\/MM study of thyroid and steroid hormone analogue interactions with alphavbeta3 integrin","volume":"2012","year":"2012","journal-title":"Journal of Biomedicine & Biotechnology"},{"key":"ref161","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1152\/ajpcell.00305.2008","article-title":"Thyroxine vs triiodo thyronine and cell proliferation : activation of mitogen - activated protein kinase and phosphatidylinositol kinase of https org","volume":"5","year":"2009","journal-title":"American Journal Physiology Cell Physiology"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1083\/jcb.130.2.451","article-title":"CD31\/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium","volume":"130","year":"1995","journal-title":"Journal of Cell Biology"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/pros.20725","article-title":"Triiodothyronine modulates cell proliferation of human prostatic carcinoma cells by downregulation of the B-cell translocation gene 2","volume":"68","year":"2008","journal-title":"Prostate"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"e79633","DOI":"10.1371\/journal.pone.0079633","article-title":"Eicosanoid profiling in an orthotopic model of lung cancer progression by mass spectrometry demonstrates selective production of leukotrienes by inflammatory cells of the microenvironment","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1182\/blood-2004-04-1358","article-title":"Stimulation of endothelial cell proliferation by FGF-2 in the presence of fibrinogen requires alphavbeta3","volume":"104","year":"2004","journal-title":"Blood"},{"key":"ref101","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1073\/pnas.1706801115","article-title":"thyroid hormone signaling mediates cardiometabolic effects in vivo https org","author":"Noncanonical","year":"2017"},{"key":"ref301","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1136\/ard.61.suppl_2.ii96","article-title":"alpha beta as a target for treatment of rheumatoid arthritis and related rheumatic diseases of the Supplement ii ii https org","author":"WilderRL","year":"2002","journal-title":"Annals Rheumatic Diseases"},{"key":"ref121","first-page":"e1375642","article-title":"Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer","volume":"7","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1379\/1466-1268(2003)8<37:IVRFVA>2.0.CO;2","article-title":"Integrin alphavbeta3, requirement for VEGFR2-mediated activation of SAPK2\/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF","volume":"8","year":"2003","journal-title":"Cell Stress & Chaperones"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/CEJ.0b013e3280145c00","article-title":"The role of adhesion molecules, alpha v beta 3, alpha v beta 5 and their ligands in the tumor cell and endothelial cell adhesion","volume":"16","year":"2007","journal-title":"European Journal of Cancer Prevention"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/annonc\/mdw640","article-title":"Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer","volume":"28","year":"2017","journal-title":"Annals of Oncology"},{"key":"ref141","first-page":"3515","article-title":"Enhancing effect of thyroxine on tumor growth and metastases in syngeneic mouse tumor systems","volume":"39","year":"1979","journal-title":"Cancer Research"},{"key":"ref111","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1530\/EJE-14-0198","article-title":"side - effects of anti - cancer drugs : thyroid effects of tyrosine kinase inhibitors of https org","year":"2014","journal-title":"Endocrine European Journal Endocrinology"},{"key":"ref151","first-page":"62","article-title":"Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated","volume":"29","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"e27547","DOI":"10.1371\/journal.pone.0027547","article-title":"Crosstalk between integrin alphavbeta3 and estrogen receptor-alpha is involved in thyroid hormone-induced proliferation in human lung carcinoma cells","volume":"6","year":"2011","journal-title":"PLoS One"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/26\/6\/ERC-18-0353.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/26\/6\/ERC-18-0353.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:04Z","timestamp":1784555704000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/26\/6\/565-574\/35033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":31,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/erc-18-0353","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6]]}}}