Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance
Ovarian Cancer (OVCA) is the most fatal gynecologic cancer and has a 5-year survival rate less than 45%. This is mainly due to late diagnosis and drug resistance. Overexpression of plasma gelsolin (pGSN) is key contributing factor to OVCA chemoresistance and immunosuppression. Gelsolin (GSN) is a mu...
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MDPI AG
2022-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/20/3305 |
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| author | Toshimichi Onuma Meshach Asare-Werehene Yoshio Yoshida Benjamin K. Tsang |
| author_facet | Toshimichi Onuma Meshach Asare-Werehene Yoshio Yoshida Benjamin K. Tsang |
| author_sort | Toshimichi Onuma |
| collection | DOAJ |
| description | Ovarian Cancer (OVCA) is the most fatal gynecologic cancer and has a 5-year survival rate less than 45%. This is mainly due to late diagnosis and drug resistance. Overexpression of plasma gelsolin (pGSN) is key contributing factor to OVCA chemoresistance and immunosuppression. Gelsolin (GSN) is a multifunctional protein that regulates the activity of actin filaments by cleavage, capping, and nucleation. Generally, it plays an important role in cytoskeletal remodeling. GSN has three isoforms: cytosolic GSN, plasma GSN (pGSN), and gelsolin-3. Exosomes containing pGSN are released and contribute to the progression of OVCA. This review describes how pGSN overexpression inhibits chemotherapy-induced apoptosis and triggers positive feedback loops of pGSN expression. It also describes the mechanisms by which exosomal pGSN promotes apoptosis and dysfunction in tumor-killing immune cells. A discussion on the potential of pGSN as a prognostic, diagnostic, and therapeutic marker is also presented herein. |
| first_indexed | 2024-03-09T20:29:30Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:29:30Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cb41517c41f046f4839cb060376cfc9b2023-11-23T23:28:55ZengMDPI AGCells2073-44092022-10-011120330510.3390/cells11203305Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of ChemoresistanceToshimichi Onuma0Meshach Asare-Werehene1Yoshio Yoshida2Benjamin K. Tsang3Department of Obstetrics & Gynecology, Faculty of Medicine & Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8L1, CanadaDepartment of Obstetrics & Gynecology, Faculty of Medicine & Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8L1, CanadaDepartment of Obstetrics and Gynecology, University of Fukui, Fukui 910-8507, JapanDepartment of Obstetrics & Gynecology, Faculty of Medicine & Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1H 8L1, CanadaOvarian Cancer (OVCA) is the most fatal gynecologic cancer and has a 5-year survival rate less than 45%. This is mainly due to late diagnosis and drug resistance. Overexpression of plasma gelsolin (pGSN) is key contributing factor to OVCA chemoresistance and immunosuppression. Gelsolin (GSN) is a multifunctional protein that regulates the activity of actin filaments by cleavage, capping, and nucleation. Generally, it plays an important role in cytoskeletal remodeling. GSN has three isoforms: cytosolic GSN, plasma GSN (pGSN), and gelsolin-3. Exosomes containing pGSN are released and contribute to the progression of OVCA. This review describes how pGSN overexpression inhibits chemotherapy-induced apoptosis and triggers positive feedback loops of pGSN expression. It also describes the mechanisms by which exosomal pGSN promotes apoptosis and dysfunction in tumor-killing immune cells. A discussion on the potential of pGSN as a prognostic, diagnostic, and therapeutic marker is also presented herein.https://www.mdpi.com/2073-4409/11/20/3305plasma gelsolin (pGSN)extracellular vesicles (EVs)chemoresistancetumor microenvironment (TME)ovarian cancerimmune cells |
| spellingShingle | Toshimichi Onuma Meshach Asare-Werehene Yoshio Yoshida Benjamin K. Tsang Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance Cells plasma gelsolin (pGSN) extracellular vesicles (EVs) chemoresistance tumor microenvironment (TME) ovarian cancer immune cells |
| title | Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance |
| title_full | Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance |
| title_fullStr | Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance |
| title_full_unstemmed | Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance |
| title_short | Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance |
| title_sort | exosomal plasma gelsolin is an immunosuppressive mediator in the ovarian tumor microenvironment and a determinant of chemoresistance |
| topic | plasma gelsolin (pGSN) extracellular vesicles (EVs) chemoresistance tumor microenvironment (TME) ovarian cancer immune cells |
| url | https://www.mdpi.com/2073-4409/11/20/3305 |
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