{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:23:04Z","timestamp":1787664184880,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017590","name":"University Hospital Essen","doi-asserted-by":"publisher","award":["IFORES D\/107"],"award-info":[{"award-number":["IFORES D\/107"]}],"id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glioblastoma (GBM) is characterized by extensive neo-angiogenesis, which drives rapid tumor growth and therapeutic resistance. We previously identified PDCD10 as a tumor suppressor in GBM. Here, we investigated whether PDCD10 loss promotes neo-angiogenesis through paracrine signaling and GBM cell plasticity. PDCD10 knockdown (shPDCD10) enhanced endothelial angiogenic activity after treatment with conditioned medium (CM) from shPDCD10 cells and in a direct co-culture model. Moreover, application of CM to the chicken chorioallantoic membrane increased vascular branching in an in vivo angiogenesis model. Antibody array analysis detected elevated levels of multiple pro-angiogenic factors following PDCD10 depletion. In a GBM mouse model, shPDCD10 tumors exhibited pronounced hypervascularity and stromal expansion. Indeed, immunofluorescence revealed colocalization of CD31 with the tumor cell reporter RFP in a subset of implanted shPDCD10 GBM cells, suggesting that these tumor cells acquired an endothelial molecular signature. PDCD10 loss also promoted a glioma stem cell (GSC)-like phenotype, characterized by enhanced clonogenicity, sphere formation, and upregulation of Nestin, KLF4, and SOX2. Under endothelial induction conditions, shPDCD10 sphere-derived cells exhibited endothelial-like characters, showing greater tube-forming capacity and increased Ac-LDL uptake. Taken together, these findings demonstrate that PDCD10 loss promotes GBM neo-angiogenesis involving complementary paracrine and GSC-like plasticity mechanisms, highlighting PDCD10 as a potential therapeutic target to suppress neo-angiogenesis in GBM.<\/jats:p>","DOI":"10.3390\/cells15171532","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:57:17Z","timestamp":1787662637000},"page":"1532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PDCD10-Deficient Tumor Cells Reprogram Angiogenesis Through Paracrine Endothelial Activation and GSC-like Plasticity in GBM"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhong-Rong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Yan","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9651-031X","authenticated-orcid":false,"given":"Maike Anna","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-0644","authenticated-orcid":false,"given":"Nicole","family":"D\u00fcnker","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy, Medical Faculty, Institute of Anatomy II, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-4298","authenticated-orcid":false,"given":"Laur\u00e8l","family":"Rauschenbach","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-1821","authenticated-orcid":false,"given":"Ulrich","family":"Sure","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-0768","authenticated-orcid":false,"given":"Yuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-024-00516-y","article-title":"Glioma","volume":"10","author":"Weller","year":"2024","journal-title":"Nat. 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