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The EGFR signaling system is well characterized in immortalized cell lines such as HeLa derived from tumor tissues, but much less is known about EGFR function in untransformed multipotent stromal\/stem cells (MSCs). We compared the effect of epidermal growth factor (EGF), transforming growth factor-\u03b1 (TGF-\u03b1) and amphiregulin (AREG) on physiological responses in endometrial MSCs (enMSC) and HeLa cells. In addition, using Western blotting and confocal microscopy, we studied the internalization and degradation of EGFR stimulated by the three ligands in these cell lines. We demonstrated that unlike HeLa, EGF and TGF-\u03b1, but not AREG, stimulated enMSC proliferation and prevented decidual differentiation in an EGFR-dependent manner. In HeLa cells, EGF targeted EGFR for degradation, while TGF-\u03b1 stimulated its recycling. Surprisingly, in enMSC, both ligands caused EGFR degradation. In both cell lines, AREG-EGFR internalization was not registered. In HeLa cells, EGFR was degraded within 2 h, restoring its level in 24 h, while in enMSC, degradation took more than 4\u20138 h, and the low EGFR level persisted for several days. This indicates that EGFR homeostasis in MSCs may differ significantly from that in immortalized cell lines.<\/jats:p>","DOI":"10.3390\/ijms241713408","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T09:44:46Z","timestamp":1693388686000},"page":"13408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["EGF, TGF-\u03b1 and Amphiregulin Differently Regulate Endometrium-Derived Mesenchymal Stromal\/Stem Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-1577","authenticated-orcid":false,"given":"Rimma Sergeevna","family":"Kamentseva","sequence":"first","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-5072","authenticated-orcid":false,"given":"Marianna Viktorovna","family":"Kharchenko","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnara Vladikovna","family":"Gabdrahmanova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7422-6807","authenticated-orcid":false,"given":"Michael Alexandrovich","family":"Kotov","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"},{"name":"Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, Hlopina St. 11, St. Petersburg 195251, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9221-9362","authenticated-orcid":false,"given":"Vera Vladislavovna","family":"Kosheverova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2951-6292","authenticated-orcid":false,"given":"Elena Sergeevna","family":"Kornilova","sequence":"additional","affiliation":[{"name":"Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russia"},{"name":"Faculty of Biology, St. Petersburg State University, 7-9 Universitetskaya Embankment, St. Petersburg 199034, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2008.12.008","article-title":"Wnt signaling controls the fate of mesenchymal stem cells","volume":"433","author":"Ling","year":"2009","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/stem.319","article-title":"Transforming Growth Factor-\u03b2 and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells","volume":"28","author":"Kurpinski","year":"2010","journal-title":"Stem Cells"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"599276","DOI":"10.3389\/fcell.2020.599276","article-title":"The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche","volume":"8","author":"Bazzoni","year":"2021","journal-title":"Front. 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