{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T03:28:35Z","timestamp":1776310115103,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"AIRC (Associazione Italiana Ricerca Cancro)","doi-asserted-by":"publisher","award":["IG 2022-27540"],"award-info":[{"award-number":["IG 2022-27540"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"AIRC (Associazione Italiana Ricerca Cancro)","doi-asserted-by":"publisher","award":["2022CZR88M"],"award-info":[{"award-number":["2022CZR88M"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Progetti di Ricerca di Interesse Nazionale (PRIN)","award":["IG 2022-27540"],"award-info":[{"award-number":["IG 2022-27540"]}]},{"name":"Progetti di Ricerca di Interesse Nazionale (PRIN)","award":["2022CZR88M"],"award-info":[{"award-number":["2022CZR88M"]}]},{"name":"Italian Ministry of Health to Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","award":["IG 2022-27540"],"award-info":[{"award-number":["IG 2022-27540"]}]},{"name":"Italian Ministry of Health to Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico","award":["2022CZR88M"],"award-info":[{"award-number":["2022CZR88M"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984\u2019s antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (\u221240.8 (17.08)%, p &lt; 0.001 vs. basal, n = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, p &lt; 0.001 vs. basal, n = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.<\/jats:p>","DOI":"10.3390\/ijms25073606","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:47:11Z","timestamp":1711370831000},"page":"3606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Novel SSTR3 Agonist ITF2984 Exerts Antimitotic and Proapoptotic Effects in Human Non-Functioning Pituitary Neuroendocrine Tumor (NF-PitNET) Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Genesio","family":"Di Muro","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"Department of Experimental Medicine, University Sapienza of Rome, 00100 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Catalano","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Treppiedi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-7512","authenticated-orcid":false,"given":"Anna Maria","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Mangili","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giusy","family":"Marra","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Di Bari","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"PhD Program in Experimental Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1573-036X","authenticated-orcid":false,"given":"Emma","family":"Nozza","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"PhD Program in Experimental Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea G.","family":"Lania","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy"},{"name":"Endocrinology and Diabetology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, 20089 Rozzano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-7650","authenticated-orcid":false,"given":"Emanuele","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Modena","sequence":"additional","affiliation":[{"name":"Preclinical R&D, Italfarmaco Group, Cinisello Balsamo, 20092 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Steinkuhler","sequence":"additional","affiliation":[{"name":"Preclinical R&D, Italfarmaco Group, Cinisello Balsamo, 20092 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-7895","authenticated-orcid":false,"given":"Erika","family":"Peverelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-3886","authenticated-orcid":false,"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"Endocrinology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.ecl.2007.10.011","article-title":"Nonfunctioning pituitary tumors and pituitary incidentalomas","volume":"37","author":"Molitch","year":"2008","journal-title":"Endocrinol. 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