{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:52:53Z","timestamp":1790455973829,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid cancers with limited treatment options and poor prognosis. While the tumor microenvironment (TME), especially cancer-associated fibroblasts (CAFs), is known to support tumor growth, its metabolic role is not well understood. This study aimed to investigate the role of type 2 deiodinase (D2)\u2014an enzyme converting thyroxine to active triiodothyronine (T3)\u2014in sustaining a pro-tumorigenic TME in PDTC and ATC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We analyzed D2 expression in both thyroid cancer epithelial cells and CAFs, including inflammatory CAFs (iCAFs), using murine and human PDTC\/ATC models. Functional relevance was assessed through pharmacological inhibition of D2 in mouse xenograft models and coculture three-dimensional (3D) spheroids. The effects on tumor growth, CAF composition, and epithelial\u2013stromal signaling were evaluated. In addition, human PDTC-derived organoids were used to test responsiveness to thyroid hormone (TH) modulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      D2 was found to be highly expressed in CAFs, particularly iCAFs, exceeding levels observed in cancer epithelial cells.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      inhibition of D2 led to reduced tumor growth and changes in CAF profiles and activation. In 3D coculture spheroids, D2 activity was essential for tumor cell proliferation via a paracrine loop that enhanced local TH signaling. Human PDTC organoids expressing D2 also responded to TH modulation, confirming a positive effect of T3 on tumoral growth in this context.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We identified D2 as a key mediator of stromal\u2013epithelial cross talk in PDTC and ATC and highlight local TH metabolism as a potential therapeutic target in these lethal cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10507256251401458","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T14:51:52Z","timestamp":1764687112000},"page":"71-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Type 2 Deiodinase in Cancer-Associated Fibroblasts is Required to Sustain Growth of Poorly and Undifferentiated Thyroid Cancer"],"prefix":"10.1177","volume":"36","author":[{"given":"Maria Angela","family":"De Stefano","sequence":"first","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Luongo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Porcelli","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costantina","family":"Cervone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Passarella","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Spiezia","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Local Health Authority Naples 1 Center, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Misso","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Local Health Authority Naples 1 Center, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Cerbone","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate Franco Salvatore, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Carillo","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schlumberger","sequence":"additional","affiliation":[{"name":"Gustave Roussy, D\u00e9partement d\u2019Imagerie M\u00e9dicale, Service de Canc\u00e9rologie Endocrinienne, Paris-Saclay University, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Naples \u201cFederico II\u201d, Naples, Italy."},{"name":"CEINGE Biotecnologie Avanzate Franco Salvatore, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.26348"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00598-y"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34395-2"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2024.0266"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102043"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18916-5"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01013-0"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173712"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-00986-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00275"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-23-0015"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab016"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab059"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-10-0448"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706754104"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.042"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0031"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-23-0016"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36755-y"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13140-2"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1698"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaf050"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404357111"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0735"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169653"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-22-0269"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115432"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-024-10181-y"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-15-0162"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.703730"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.1.0455"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602222200"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2A0114-048RR"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-16-0483"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-08-0036"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022567"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00053"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.01.003"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-2066"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85271"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-024-02526-9"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14100"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10507256251401458","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10507256251401458","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10507256251401458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:10:32Z","timestamp":1787065832000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10507256251401458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"alternative-id":["10.1177\/10507256251401458"],"URL":"https:\/\/doi.org\/10.1177\/10507256251401458","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.07.10.664131","asserted-by":"object"}]},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]}}}