{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:31:37Z","timestamp":1785295897007,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Czech Agency for Healthcare Research (AZV)","award":["AZV NV19-01-00083"],"award-info":[{"award-number":["AZV NV19-01-00083"]}]},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["Progress Q26, SVV 260 521, UNCE\/MED\/016"],"award-info":[{"award-number":["Progress Q26, SVV 260 521, UNCE\/MED\/016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and non-glycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 \u201ctumor enriched\u201d proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.<\/jats:p>","DOI":"10.3390\/molecules26216567","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:22:24Z","timestamp":1635805344000},"page":"6567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-0699","authenticated-orcid":false,"given":"Ondrej","family":"Vit","sequence":"first","affiliation":[{"name":"BIOCEV, First Faculty of Medicine, Charles University, 25250 Vestec, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayank","family":"Patel","sequence":"additional","affiliation":[{"name":"Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Musil","sequence":"additional","affiliation":[{"name":"Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 12800 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Frysak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Miettinen","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-4803","authenticated-orcid":false,"given":"Jiri","family":"Petrak","sequence":"additional","affiliation":[{"name":"BIOCEV, First Faculty of Medicine, Charles University, 25250 Vestec, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3389\/fendo.2018.00515","article-title":"Update of Pheochromocytoma Syndromes: Genetics, Biochemical Evaluation, and Imaging","volume":"9","author":"Alrezk","year":"2018","journal-title":"Front. 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