Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients
Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most impo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/13/10922 |
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| author | Montalbano Mauro Perricone Ugo Zachary Walton Shirafkan Ali Cristiana Rastellini Luca Cicalese |
| author_facet | Montalbano Mauro Perricone Ugo Zachary Walton Shirafkan Ali Cristiana Rastellini Luca Cicalese |
| author_sort | Montalbano Mauro |
| collection | DOAJ |
| description | Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis. |
| first_indexed | 2024-03-11T01:39:14Z |
| format | Article |
| id | doaj.art-926e60df30004bc685a32b5bf465f791 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T01:39:14Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-926e60df30004bc685a32b5bf465f7912023-11-18T16:45:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131092210.3390/ijms241310922Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma PatientsMontalbano Mauro0Perricone Ugo1Zachary Walton2Shirafkan Ali3Cristiana Rastellini4Luca Cicalese5Department of Neurology, University of Texas Medical Branch, Galveston, TX 77555-5302, USAMolecular Informatics Group, Fondazione Ri.MED., 90133 Palermo, ItalyJohn Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX 77555-5302, USARutgers Health, Department of Cardiac Surgery, New Brunswick, NJ 08901, USADepartment of Surgery, University of Texas Medical Branch, Galveston, TX 77555-5302, USADepartment of Neurobiology, University of Texas Medical Branch, Galveston, TX 77555-5302, USAGlypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis.https://www.mdpi.com/1422-0067/24/13/10922hepatocellular carcinomaGlypican-3small extracellular vesicleserum marker |
| spellingShingle | Montalbano Mauro Perricone Ugo Zachary Walton Shirafkan Ali Cristiana Rastellini Luca Cicalese Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients International Journal of Molecular Sciences hepatocellular carcinoma Glypican-3 small extracellular vesicle serum marker |
| title | Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients |
| title_full | Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients |
| title_fullStr | Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients |
| title_full_unstemmed | Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients |
| title_short | Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients |
| title_sort | glypican 3 gpc 3 structural analysis and cargo in serum small extracellular vesicles of hepatocellular carcinoma patients |
| topic | hepatocellular carcinoma Glypican-3 small extracellular vesicle serum marker |
| url | https://www.mdpi.com/1422-0067/24/13/10922 |
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