{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:45:04Z","timestamp":1788576304734,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"DFG-funded Research Center","doi-asserted-by":"publisher","award":["SFB1324\/1"],"award-info":[{"award-number":["SFB1324\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"DFG-funded Research Center","doi-asserted-by":"publisher","award":["GR4810\/2-1"],"award-info":[{"award-number":["GR4810\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Medical Center G\u00f6ttingen","award":["SFB1324\/1"],"award-info":[{"award-number":["SFB1324\/1"]}]},{"name":"University Medical Center G\u00f6ttingen","award":["GR4810\/2-1"],"award-info":[{"award-number":["GR4810\/2-1"]}]},{"name":"Health and Medical University Potsdam","award":["SFB1324\/1"],"award-info":[{"award-number":["SFB1324\/1"]}]},{"name":"Health and Medical University Potsdam","award":["GR4810\/2-1"],"award-info":[{"award-number":["GR4810\/2-1"]}]},{"name":"University Medical Center G\u00f6ttingen (UMG)\u2019s Core Facility Proteomics","award":["SFB1324\/1"],"award-info":[{"award-number":["SFB1324\/1"]}]},{"name":"University Medical Center G\u00f6ttingen (UMG)\u2019s Core Facility Proteomics","award":["GR4810\/2-1"],"award-info":[{"award-number":["GR4810\/2-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumor-derived extracellular vesicles (EVs) play an important role in cancer progression. Neutral sphingomyelinases (nSMases) are lipid-modifying enzymes that modulate the secretion of EVs from cells. How nSMase activity and therefore ceramide generation affect the composition and functionality of secreted EVs is not fully understood. Here, we aimed to investigate the expression of nSMases 1 and 2 in prostate cancer (PCa) tissue and their role in EV composition and secretion for prostate cancer cell migration. Reduced nSMase 1 and 2 expression was found in prostate cancer and correlated with the age of the patient. When nSMase 2 was inhibited by GW4869 in PCa cells (PC3 and DU145), the EV secretome was significantly altered, while the number of EVs and the total protein content of released EVs were not significantly changed. Using proteomic analysis, we found that extracellular matrix proteins, such as SDC4 (Syndecan-4) and SRPX-2, were differentially secreted on EVs from GW4869-treated PC3 cells. In scratch wound migration assays, GW4869 significantly increased migration compared to control PC3 cells but not DU145 cells, while SDC4 knockdown significantly reduced the migration of PC3 cells. These and other nSMase-2-dependent secreted proteins are interesting candidates for understanding the role of stress-induced EVs in the progression of prostate cancer.<\/jats:p>","DOI":"10.3390\/cells14070547","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Ceramide-Dependent EV Secretome Differentially Affects Prostate Cancer Cell Migration"],"prefix":"10.3390","volume":"14","author":[{"given":"Dolma","family":"Choezom","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Department of Developmental Biochemistry, University Medical Center Goettingen, 37077 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Moritz","family":"Plum","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Department of Developmental Biochemistry, University Medical Center Goettingen, 37077 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-7407","authenticated-orcid":false,"given":"Pradhipa","family":"Karuna M.","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Department of Developmental Biochemistry, University Medical Center Goettingen, 37077 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7337-3797","authenticated-orcid":false,"given":"Adi","family":"Danieli-Mackay","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Department of Developmental Biochemistry, University Medical Center Goettingen, 37077 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0946-8166","authenticated-orcid":false,"given":"Christof","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Center Goettingen, 37075 Goettingen, Germany"},{"name":"Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, 37077 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-2828","authenticated-orcid":false,"given":"Phillipp","family":"Brockmeyer","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-5664","authenticated-orcid":false,"given":"Julia Christina","family":"Gross","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, Department Medicine, HMU Health and Medical University Potsdam, 14471 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2300021","DOI":"10.1002\/pmic.202300021","article-title":"The multifaceted roles of small extracellular vesicles in metabolic reprogramming in the tumor microenvironments","volume":"24","author":"Chen","year":"2024","journal-title":"Proteomics"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Conteduca, V., Gurioli, G., Brighi, N., Lolli, C., Schepisi, G., Casadei, C., Burgio, S.L., Gargiulo, S., Ravaglia, G., and Rossi, L. 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