Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma
High-grade serous ovarian carcinoma (HGSOC) is a deadly subtype of ovarian cancer (OC), often diagnosed at late stages due to nonspecific symptoms and lack of effective markers for early detection. Aberrant protein N-linked glycosylation has been reported in HGSOC, holding a potential for improving...
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Elsevier
2025-01-01
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| Series: | BBA Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667160325000031 |
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| author | Kristina Mae Bienes Akira Yokoi Masami Kitagawa Hiroaki Kajiyama Morten-Thaysen Andersen Rebeca Kawahara |
| author_facet | Kristina Mae Bienes Akira Yokoi Masami Kitagawa Hiroaki Kajiyama Morten-Thaysen Andersen Rebeca Kawahara |
| author_sort | Kristina Mae Bienes |
| collection | DOAJ |
| description | High-grade serous ovarian carcinoma (HGSOC) is a deadly subtype of ovarian cancer (OC), often diagnosed at late stages due to nonspecific symptoms and lack of effective markers for early detection. Aberrant protein N-linked glycosylation has been reported in HGSOC, holding a potential for improving the diagnosis and prognosis of affected patients. Building on our recent observation documenting that HGSOC-derived extracellular vesicles (EVs) exhibit aberrant protein expression patterns, we here explore the protein N-glycosylation displayed by EVs isolated from HGSOC cell lines and patient ascites relative to those from matching controls to unveil candidate markers for HGSOC. Comparative glycoproteomics of small EVs (sEVs, <200 nm) and medium/large EVs (m/lEVs, >200 nm) isolated from HGSOC and non-cancerous cell lines revealed lower overall N-glycosylation of EV proteins and a decreased protein expression of oligosaccharyltransferase (OST) subunits from HGSOC compared to non-cancerous cell lines. Increased α2,6-sialylation was also observed in m/lEVs from HGSOC cell lines and patient ascites by lectin blotting, which correlated with increased gene expression of ST6GAL1 and decreased gene expression of ST3GAL3/4 in HGSOC compared to normal ovary tissues. Our study provides insights into the EV glycoproteome of HGSOC and the underlying changes in the glycosylation machinery in HGSOC tissues, opening new avenues for the discovery of novel markers against HGSOC. |
| format | Article |
| id | doaj-art-2648d72ce0874fbca09113f69a8cb298 |
| institution | Kabale University |
| issn | 2667-1603 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | BBA Advances |
| spelling | doaj-art-2648d72ce0874fbca09113f69a8cb2982025-01-23T05:27:54ZengElsevierBBA Advances2667-16032025-01-017100140Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinomaKristina Mae Bienes0Akira Yokoi1Masami Kitagawa2Hiroaki Kajiyama3Morten-Thaysen Andersen4Rebeca Kawahara5Institute for Glyco-core Research (iGCORE), Nagoya University, Emergent/Innovative Engineering Building Room 815, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; Nagoya University Institute for Advanced Research, Japan; Co-corresponding author.Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanInstitute for Glyco-core Research (iGCORE), Nagoya University, Emergent/Innovative Engineering Building Room 815, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan; School of Natural Sciences, Macquarie University, AustraliaInstitute for Glyco-core Research (iGCORE), Nagoya University, Emergent/Innovative Engineering Building Room 815, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan; Corresponding author.High-grade serous ovarian carcinoma (HGSOC) is a deadly subtype of ovarian cancer (OC), often diagnosed at late stages due to nonspecific symptoms and lack of effective markers for early detection. Aberrant protein N-linked glycosylation has been reported in HGSOC, holding a potential for improving the diagnosis and prognosis of affected patients. Building on our recent observation documenting that HGSOC-derived extracellular vesicles (EVs) exhibit aberrant protein expression patterns, we here explore the protein N-glycosylation displayed by EVs isolated from HGSOC cell lines and patient ascites relative to those from matching controls to unveil candidate markers for HGSOC. Comparative glycoproteomics of small EVs (sEVs, <200 nm) and medium/large EVs (m/lEVs, >200 nm) isolated from HGSOC and non-cancerous cell lines revealed lower overall N-glycosylation of EV proteins and a decreased protein expression of oligosaccharyltransferase (OST) subunits from HGSOC compared to non-cancerous cell lines. Increased α2,6-sialylation was also observed in m/lEVs from HGSOC cell lines and patient ascites by lectin blotting, which correlated with increased gene expression of ST6GAL1 and decreased gene expression of ST3GAL3/4 in HGSOC compared to normal ovary tissues. Our study provides insights into the EV glycoproteome of HGSOC and the underlying changes in the glycosylation machinery in HGSOC tissues, opening new avenues for the discovery of novel markers against HGSOC.http://www.sciencedirect.com/science/article/pii/S2667160325000031N-glycansGlycoproteinsExtracellular vesiclesHigh grade serous carcinomaBiomarkerGlycoproteomics |
| spellingShingle | Kristina Mae Bienes Akira Yokoi Masami Kitagawa Hiroaki Kajiyama Morten-Thaysen Andersen Rebeca Kawahara Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma BBA Advances N-glycans Glycoproteins Extracellular vesicles High grade serous carcinoma Biomarker Glycoproteomics |
| title | Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma |
| title_full | Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma |
| title_fullStr | Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma |
| title_full_unstemmed | Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma |
| title_short | Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma |
| title_sort | extracellular vesicles display distinct glycosignatures in high grade serous ovarian carcinoma |
| topic | N-glycans Glycoproteins Extracellular vesicles High grade serous carcinoma Biomarker Glycoproteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2667160325000031 |
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