{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:06:17Z","timestamp":1792789577449,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MOVIE"},{"name":"RESIDUOPINTOSORRENTINO"},{"name":"FARB2021"},{"name":"FARB2022"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sex is a biological variable that can reflect clinical outcomes in terms of quality of life, therapy effectiveness, responsiveness and\/or toxicity. Sphingosine-1-phosphate (S1P) is a lipidic mediator whose activity can be influenced by sex. To evaluate whether the S1P axis underlies sex \u2018instructions\u2019 in the lung during physiological and oncological lung conditions, sphingosine and S1P were quantified in the blood of healthy (H) volunteers, lung adenocarcinoma (ADK) and squamous cell carcinoma (SCC) patients of both sexes. S1P receptors and their metabolic enzymes were evaluated in the tissues. Circulating levels of S1P were similar among H female and male subjects and female SCC patients. Instead, male and female ADK patients had lower circulating S1P levels. S1P receptor 3 (S1PR3) was physiologically expressed in the lung, but it was overexpressed in male SCC, and female and male ADK, but not in female SCC patients, who showed a significantly reduced ceramide synthase 1 (CERS1) mRNA and an overexpression of the ceramidase (ASAH1) precursor in lung tumor tissues, compared to male SCC and both male and female ADK patients. These findings highlighted sex differences in S1P rheostat in pathological conditions, but not in physiological conditions, identifying S1P as a prognostic mediator depending on lung cancer histotype.<\/jats:p>","DOI":"10.3390\/ijms241310841","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:43:30Z","timestamp":1688085810000},"page":"10841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex Differences in Sphingosine-1-Phosphate Levels Are Dependent on Ceramide Synthase 1 and Ceramidase in Lung Physiology and Tumor Conditions"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-7603","authenticated-orcid":false,"given":"Michela","family":"Terlizzi","sequence":"first","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-0407","authenticated-orcid":false,"given":"Chiara","family":"Colarusso","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5598-7525","authenticated-orcid":false,"given":"Giusy","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Falanga","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-2909","authenticated-orcid":false,"given":"Maria Chiara","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Somma","sequence":"additional","affiliation":[{"name":"Anatomy and Pathology Unit, Ospedale dei Colli, Azienda Ospedaliera di Rilievo Nazionale (AORN), \u201cMonaldi\u201d, 84131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Anatomy and Pathology Unit, Ospedale dei Colli, Azienda Ospedaliera di Rilievo Nazionale (AORN), \u201cMonaldi\u201d, 84131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Panico","sequence":"additional","affiliation":[{"name":"Anatomy and Pathology Unit, Ospedale dei Colli, Azienda Ospedaliera di Rilievo Nazionale (AORN), \u201cMonaldi\u201d, 84131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Pinto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFARMA), University of Salerno, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1124\/jpet.116.233205","article-title":"S1P Signaling and De Novo Biosynthesis in Blood Pressure Homeostasis","volume":"358","author":"Cantalupo","year":"2016","journal-title":"J. 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