{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:23:57Z","timestamp":1787765037482,"version":"build-2784847793"},"reference-count":82,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007446","name":"King Khalid University, Kingdom of Saudi Arabia","doi-asserted-by":"publisher","award":["R.G.P. 1\/297\/46"],"award-info":[{"award-number":["R.G.P. 1\/297\/46"]}],"id":[{"id":"10.13039\/501100007446","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R.G.P. 1\/297\/46"],"award-info":[{"award-number":["R.G.P. 1\/297\/46"]}],"id":[{"id":"https:\/\/ror.org\/052kwzs30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: In our companion study, the gingival mesenchymal stem cell (GMSC) secretome suppresses oxidative stress and induces apoptosis in primary oral squamous cell carcinoma (OSCC) cells, where those wet-lab results are themselves reported as preliminary; here we ask whether it also engages a proliferation \u00d7 migration programme in patient tissue. The two arms differ in read-out type (apoptosis and redox there, transcript abundance here), not in opposed function. Methods: Primary OSCC cells received GMSC-conditioned medium (GMSC-CM) or indirect Transwell co-culture, assayed by RT-qPCR (VEGFA, TGFB1, MMP9, CXCL12, CCND1, PCNA, MYC, EGFR), MTT, and scratch-wound migration. Thirteen computational layers plus a GeoMx spatial verify-and-decide layer were applied to public data: TCGA-HNSC, GEO, CPTAC, single-cell inference, prognostic modelling, DepMap and LINCS L1000. Results: All eight transcripts were raised in all three arms (16 of 24 comparisons significant), indicating a pro-tumour transcriptional shift; metabolic activity was unchanged and wound closure was reduced under conditioned medium (p &lt; 0.01). Of 1358 genes significant in all three modalities, 1219 (89.8%, 95% CI 88.0\u201391.3%) share direction against 25.0% expected by chance (3.59-fold; exact binomial p below machine precision). The pre-registered oral-cavity signature did not validate externally (GSE41613; C = 0.562), and no ligand\u2013receptor pair survived permutation calibration. Conclusions: GMSC paracrine exposure induces a pro-tumour transcriptional programme in primary OSCC cells that replicates at patient level, without demonstrated functional or therapeutic consequence; gefitinib is nominated only as a hypothesis-generating candidate. The evidence rests on three primary cultures (n = 3), one GMSC donor preparation, one 24 h time point, a single reference gene, no cell-line authentication and no test of gefitinib; the study programme has concluded, and these experiments cannot be performed now.<\/jats:p>","DOI":"10.3390\/cells15171538","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:54:42Z","timestamp":1787763282000},"page":"1538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Dual Face of Gingival Mesenchymal Stem Cell Paracrine Signalling in Oral Squamous Cell Carcinoma: A Pro-Tumour Transcriptional Programme and a Hypothesis-Generating Drug-Repurposing Screen"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0564-0616","authenticated-orcid":false,"given":"Abdullah","family":"Alqarni","sequence":"first","affiliation":[{"name":"Department of Oral Diagnosis, Oral Biology & Periodontology, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3579-0906","authenticated-orcid":false,"given":"Jagadish","family":"Hosmani","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Oral Biology & Periodontology, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7013-2808","authenticated-orcid":false,"given":"Saeed","family":"Arem","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Science and Oral Biology, College of Dentistry, King Khalid University, P.O. Box 960, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Almubarak","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Oral Biology & Periodontology, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Ahmed","family":"Assiri","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Oral Biology & Periodontology, College of Dentistry, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3080-2775","authenticated-orcid":false,"given":"Rayan Mohammedfarooq","family":"Meer","sequence":"additional","affiliation":[{"name":"Department of Preventive Dental Sciences, College of Dentistry, Taibah University, Madinah 42353, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-5497","authenticated-orcid":false,"given":"Shankargouda","family":"Patil","sequence":"additional","affiliation":[{"name":"College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT 84095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/154405910808700104","article-title":"Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy","volume":"87","author":"Choi","year":"2008","journal-title":"J. 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