Recapitulating thyroid cancer histotypes through engineering embryonic stem cells.

Autor: Veschi V; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy., Turdo A; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Modica C; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy., Verona F; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Di Franco S; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy., Gaggianesi M; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy., Tirrò E; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy.; Department of Clinical and Experimental Medicine, A.O.U. Policlinico-Vittorio Emanuele, Center of Experimental Oncology and Hematology, University of Catania, Catania, Italy., Di Bella S; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Iacono ML; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Pantina VD; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy., Porcelli G; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Mangiapane LR; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Bianca P; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Rizzo A; Villa Sofia-Cervello Hospital, Palermo, Italy., Sciacca E; Queen Mary University, Experimental Medicine & Rheumatology, London, United Kingdom., Pillitteri I; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Vella V; Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy., Belfiore A; Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy., Bongiorno MR; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Pistone G; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy., Memeo L; Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Catania, Italy., Colarossi L; Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Catania, Italy., Giuffrida D; Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Catania, Italy., Colarossi C; Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, Catania, Italy., Vigneri P; Department of Clinical and Experimental Medicine, A.O.U. Policlinico-Vittorio Emanuele, Center of Experimental Oncology and Hematology, University of Catania, Catania, Italy., Todaro M; Department of Health Promotion Sciences, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.; A.O.U.P. 'Paolo Giaccone', University of Palermo, Palermo, Italy., Stassi G; Department of Surgical Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy. giorgio.stassi@unipa.it.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 11; Vol. 14 (1), pp. 1351. Date of Electronic Publication: 2023 Mar 11.
DOI: 10.1038/s41467-023-36922-1
Abstrakt: Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAF V600E or NRAS Q61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53 R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs.
(© 2023. The Author(s).)
Databáze: MEDLINE
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