{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:32:54Z","timestamp":1781105574644,"version":"3.54.1"},"reference-count":15,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Avera Cancer Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer-associated fibroblasts (CAFs) within a solid tumor can support the progression of cancer. We studied the identification and characterization of patient-derived endometrial CAFs in the context of their clinical relevance in endometrial cancers. We established patient-derived primary cultures of CAFs from surgically resected tumors (TCAF) and tumor-adjacent normal (NCAF) tissues in 53 consented patients with success rates of 97.7% and 75%, respectively. A passage of CAF was qualified by the (1) absence of CK 8,18,19, EpCAM, CD45, and CD31, and (2) presence of SMAalpha, S100A4, CD90, FAP, TE-7, CD155, PD-L1, TGFB, PDGFRA (qRT-PCR, flow cytometry, Western blot, ICC). Out of the 44 established CAFs, 31 were aggressive (having an early, i.e., 4\u20137 week, establishment time and\/or &gt;3 passages) compared to 13 which were non-aggressive. A post-surgery-event (PSE) was observed in 7 out of 31 patients bearing aggressive CAFs, 2 of whom were also positive for CTCs, while none of the 13 patients bearing non-aggressive CAFs had events. A positive correlation was found between patients with grade 3 (p = 0.025) as well as stage 3\/4 diseases (p = 0.0106) bearing aggressive CAFs and the PSE. Finally, aggressive TCAFs from patients with PSE resisted the effects of paclitaxel and lenvatinib on the growth of HUVEC and endometrial tumor cells. Our study is the first to report a correlation between the PSE and the aggressive nature of CAFs in endometrial cancers and provides an undeniable reason to study the in-depth mechanism of CAF function towards the development of treatment resistance in endometrial cancers.<\/jats:p>","DOI":"10.3390\/ijms24076449","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T02:23:46Z","timestamp":1680143026000},"page":"6449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization and Clinical Relevance of Endometrial CAFs: Correlation between Post-Surgery Event and Resistance to Drugs"],"prefix":"10.3390","volume":"24","author":[{"given":"Raed","family":"Sulaiman","sequence":"first","affiliation":[{"name":"Department of Pathology, Avera Research Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"De","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Avera Research Institute, Sioux Falls, SD 57105, USA"},{"name":"Department of Internal Medicine, University of South Dakota SSOM, USD, Sioux Falls, SD 57105, USA"},{"name":"Viecure, Greenwood Village, CO 80111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-5464","authenticated-orcid":false,"given":"Jennifer C.","family":"Aske","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Avera Research Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Lin","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Avera Research Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Dale","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Avera Research Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Gaster","sequence":"additional","affiliation":[{"name":"Assistant VP Outpatient Cancer Clinics, Avera Cancer Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Rojas","family":"Espaillat","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Avera Cancer Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Starks","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Avera Cancer Institute, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5533-8784","authenticated-orcid":false,"given":"Nandini","family":"Dey","sequence":"additional","affiliation":[{"name":"Translational Oncology Laboratory, Avera Research Institute, Sioux Falls, SD 57105, USA"},{"name":"Department of Internal Medicine, University of South Dakota SSOM, USD, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/ijgo.13866","article-title":"Cancer of the corpus uteri: 2021 update","volume":"155","author":"Koskas","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/S0140-6736(22)00323-3","article-title":"Endometrial cancer","volume":"399","author":"Crosbie","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3322\/caac.21561","article-title":"Current recommendations and recent progress in endometrial cancer","volume":"69","author":"Brooks","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1080\/14737140.2018.1491311","article-title":"Management Strategies for Recurrent Endometrial Cancer","volume":"18","author":"Connor","year":"2018","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.currproblcancer.2016.11.002","article-title":"Targeting fibroblast growth factor pathways in endometrial cancer","volume":"41","author":"Winterhoff","year":"2017","journal-title":"Curr. Probl. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1089\/omi.2020.0042","article-title":"Broadening Drug Design and Targets to Tumor Microenvironment? Cancer-Associated Fibroblast Marker Expression in Cancers and Relevance for Survival Outcomes","volume":"24","author":"Dzobo","year":"2020","journal-title":"OMICS"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pradip, D., Jennifer, A., and Nandini, D. (2021). Cancer-Associated Fibroblasts in Conversation with Tumor Cells in Endometrial Cancers: A Partner in Crime. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179121"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"De, P., Aske, J., and Dey, N. (2021). Cancer-Associated Fibroblast Functions as a Road-Block in Cancer Therapy. Cancers, 13.","DOI":"10.3390\/cancers13205246"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1158\/1078-0432.CCR-22-1031","article-title":"Cancer-associated fibroblasts in inflammation and anti-tumor immunity","volume":"29","author":"Kennel","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sulaiman, R., De, P., Aske, J.C., Lin, X., Dale, A., Vaselaar, E., Koirala, N., Ageton, C., Gaster, K., and Plorde, J. (2022). A Laboratory-Friendly CTC Identification: Comparable Double-Immunocytochemistry with Triple-Immunofluorescence. Cancers, 14.","DOI":"10.3390\/cancers14122871"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4048","DOI":"10.1200\/JCO.2001.19.20.4048","article-title":"Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: A phase II study","volume":"19","author":"Hoskins","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1056\/NEJMoa2108330","article-title":"Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer","volume":"386","author":"Makker","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1007\/s11864-022-01031-6","article-title":"Contemporary Use of Hormonal Therapy in Endometrial Cancer: A Literature Review","volume":"23","author":"Kailasam","year":"2022","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kalampokas, E., Giannis, G., Kalampokas, T., Papathanasiou, A.A., Mitsopoulou, D., Tsironi, E., Triantafyllidou, O., Gurumurthy, M., Parkin, D.E., and Cairns, M. (2022). Current Approaches to the Management of Patients with Endometrial Cancer. Cancers, 14.","DOI":"10.3390\/cancers14184500"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.18632\/oncotarget.13618","article-title":"RAC1 GTP-ase signals Wnt-beta-catenin pathway mediated integrin-directed metastasis-associated tumor cell phenotypes in triple negative breast cancers","volume":"8","author":"De","year":"2017","journal-title":"Oncotarget"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6449\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:06:28Z","timestamp":1760123188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":15,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076449"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076449","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]}}}