{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:49:15Z","timestamp":1773384555209,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH funding programs UH3 and R01","award":["UH3ES029073"],"award-info":[{"award-number":["UH3ES029073"]}]},{"name":"NIH funding programs UH3 and R01","award":["R01CA240301"],"award-info":[{"award-number":["R01CA240301"]}]},{"name":"tell every amazing lady (TEAL) award 2022","award":["UH3ES029073"],"award-info":[{"award-number":["UH3ES029073"]}]},{"name":"tell every amazing lady (TEAL) award 2022","award":["R01CA240301"],"award-info":[{"award-number":["R01CA240301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells. Oral contraceptives, tubal ligation, and salpingectomy, which are all protective against developing ovarian cancer, also decrease circulating levels of androgen. In the current study, we investigated the effect of increased testosterone on FTE and found that testosterone upregulates wingless-type MMTV integration family, member 4 (WNT4) and induces migration and invasion of immortalized human fallopian tube cells. We profiled primary human fallopian tissues grown in the microfluidic system SOLO-microfluidic platform \u2013(MFP) by RNA sequencing and found that p53 and its downstream target genes, such as paired box gene 2 (PAX2), cyclin-dependent kinase inhibitor 1A (CDK1A or p21), and cluster of differentiation 82 (CD82 or KAI1) were downregulated in response to testosterone treatment. A microfluidic platform, the PREDICT-Multi Organ System (PREDICT-MOS) was engineered to support insert technology that allowed for the study of cancer cell migration and invasion through Matrigel. Using this system, we found that testosterone enhanced FTE migration and invasion, which was reversed by the androgen receptor (AR) antagonist, bicalutamide. Testosterone also enhanced FTSEC adhesion to the ovarian stroma using murine ovaries. Overall, these results indicate that primary human fallopian tube tissue and immortalized FTSEC respond to testosterone to shift expression of genes that regulate invasion, while leveraging a new strategy to study migration in the presence of dynamic fluid flow.<\/jats:p>","DOI":"10.3390\/cancers15072062","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T01:37:02Z","timestamp":1680226622000},"page":"2062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7322-4190","authenticated-orcid":false,"given":"Angela","family":"Russo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-9864","authenticated-orcid":false,"given":"Brian P.","family":"Cain","sequence":"additional","affiliation":[{"name":"Charles Stark Draper Laboratory, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Jackson-Bey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Lopez Carrero","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Miglo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"MacLaughlan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-8804","authenticated-orcid":false,"given":"Brett C.","family":"Isenberg","sequence":"additional","affiliation":[{"name":"Charles Stark Draper Laboratory, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Coppeta","sequence":"additional","affiliation":[{"name":"Charles Stark Draper Laboratory, Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna E.","family":"Burdette","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Illinois Chicago, Chicago, IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1158\/0008-5472.CAN-16-3322","article-title":"Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium","volume":"77","author":"Ose","year":"2017","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1055\/s-2007-992926","article-title":"Polycystic ovary syndrome and endometrial cancer","volume":"26","author":"Navaratnarajah","year":"2008","journal-title":"Semin. 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