دورية أكاديمية
ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis.
| العنوان: | ISG15 mediates the function of extracellular vesicles in promoting ovarian cancer progression and metastasis. |
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| المؤلفون: | Dorayappan KDP; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Wagner V; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Park D; Molecular Genetics, Comprehensive Cancer Center The Ohio State University Wexner Medical Center Columbus Ohio USA., Newcomer MM; Department of Anatomy, School of Medicine Case Western Reserve University Cleveland Ohio USA., Lightfoot MDS; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology NYU Langone Health/Perlmutter Cancer Center New York New York USA., Kalaiyarasan D; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Sakaue T; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA.; Division of Gastroenterology, Department of Medicine Kurume University School of Medicine Kurume Japan., Khadraoui W; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Yu L; Department of Biomedical Informatics The Ohio State University Wexner Medical Center Columbus Ohio USA., Wang QE; Department of Radiation Oncology The Ohio State University Columbus Ohio USA., Maxwell GL; Inova Women's Service Line and the Inova Schar Cancer Institute Falls Church Virginia USA., O'Malley D; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Pollock RE; Division of Surgical Oncology, The James Comprehensive Cancer Center Ohio State University Columbus Ohio USA., Cohn DE; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA., Selvendiran K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology Comprehensive Cancer Center, The Ohio State University Wexner Medical Center Columbus Ohio USA. |
| المصدر: | Journal of extracellular biology [J Extracell Biol] 2024 Jan 31; Vol. 3 (2), pp. e92. Date of Electronic Publication: 2024 Jan 31 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles Country of Publication: United States NLM ID: 9918382980506676 Publication Model: eCollection Cited Medium: Internet ISSN: 2768-2811 (Electronic) Linking ISSN: 27682811 NLM ISO Abbreviation: J Extracell Biol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Hoboken, New Jersey] : Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles, [2022]- |
| مستخلص: | The interferon stimulated gene 15 (ISG15), a ubiquitin like protein and its conjugates have been implicated in various human malignancies. However, its role in ovarian cancer progression and metastasis is largely unknown. In high grade serous ovarian cancer (HGSOC), ascites is the major contributor to peritoneal metastasis. In this study, we identified significantly elevated ISG15 protein expression in HGSOC patient ascites, ascites derived primary ovarian cancer cells (POCCs), POCC small extracellular vesicles (sEVs) as well as metastatic tissue. Our results demonstrates that ISG15 increases exocytosis in ascites-derived POCCs by decreasing the endosome-lysosomal fusion, indicating a key role in sEV secretion. Further, knockdown (KD) of ISG15 resulted in a significant decrease in vesicles secretion from HGSOC cells and in vivo mouse models, leading to reduced HGSOC cell migration and invasion. Furthermore, our pre-clinical mouse model studies revealed the influence of vesicular ISG15 on disease progression and metastasis. In addition, knockdown of ISG15 or using the ISG15 inhibitor, DAP5, in combination therapy with carboplatin showed to improve the platinum sensitivity in-vitro and reduce tumour burden in-vivo. We also found that ISG15 expression within sEV represents a promising prognostic marker for HGSOC patients. Our findings suggest that ISG15 is a potential therapeutic target for inhibiting progression and metastasis in HGSOC and that vesicular ISG15 expression could be a promising biomarker in the clinical management of ovarian cancer. Significance : High-grade serous ovarian cancer (HGSOC) has high morbidity and mortality rates, but its progression and metastasis are still poorly understood, and there is an urgent need for early detection and targeted therapies. Our study presents novel findings that implicate ISG15-mediated vesicular proteins in the advancement and spread of HGSOC. These results offer pre-clinical evidence of potential new molecular targets, prognostic markers and therapeutic strategies for HGSOC that could ultimately enhance patient survival. Competing Interests: All authors declare that there are no conflicts of interest. (© 2024 The Authors. Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.) |
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| فهرسة مساهمة: | Keywords: ISG15; ISGylation; ascites; extracellular vesicles; metastasis and biomarker; ovarian cancer |
| تواريخ الأحداث: | Date Created: 20240628 Latest Revision: 20240629 |
| رمز التحديث: | 20240629 |
| مُعرف محوري في PubMed: | PMC11080709 |
| DOI: | 10.1002/jex2.92 |
| PMID: | 38939897 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2768-2811 |
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| DOI: | 10.1002/jex2.92 |