Guangyan Xie, Yongli Zhang, Jiachen Ma, Xiaoli Guo, Jiahao Xu, Linna Chen, Jingbo Zhang, Yanyu Li, Bei Zhang, Xueyan Zhou
{"title":"Exosomal AHSG in ovarian cancer ascites inhibits malignant progression of ovarian cancer by p53/FAK/Src signaling.","authors":"Guangyan Xie, Yongli Zhang, Jiachen Ma, Xiaoli Guo, Jiahao Xu, Linna Chen, Jingbo Zhang, Yanyu Li, Bei Zhang, Xueyan Zhou","doi":"10.21037/tcr-24-789","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The primary cause of mortality in patients with ovarian cancer (OC) is tumor metastasis. A comprehensive understanding of the mechanisms underlying metastasis in OC is essential for accurate prognosis prediction and the development of targeted therapeutic agents. Our findings indicate that alpha-2 Heremans Schmid glycoprotein (AHSG) is downregulated in OC exosomes. Consequently, the objective of this study was to identify novel prognostic markers and potential therapeutic targets for OC.</p><p><strong>Methods: </strong>Exosomes derived from OC cells and patient ascites were purified and applied to OC cells to assess their migratory ability using wound-healing and transwell assays. AHSG expression was enhanced by overexpressing lentivirus, and the resulting exosomes were isolated and co-cultured with OC cells to verify their effect on the migration ability of OC.</p><p><strong>Results: </strong>Exosomes in ovarian malignant ascites have been demonstrated to promote OC metastasis. However, our findings indicate that AHSG is down-regulated in OC tissues and ascites exosomes. Furthermore, overexpression of AHSG in OC cells has been shown to markedly decrease their migratory ability, as well as reduce the migratory ability of cancer cells after co-culture of its exosomes with cancer cells.</p><p><strong>Conclusions: </strong>The low expression of AHSG in exosomes derived from OC tissues and ascites is associated with metastatic progression in OC patients. Additionally, cancer-derived AHSG can be transported to OC cells via exosomes, where it inhibits OC migration <i>in vitro</i> and <i>in vivo</i> by regulating the p53/FAK/Src signaling pathway. The present study demonstrated that AHSG, derived from cancer cells, exerts a negative regulatory effect on OC cell motility, migration, and metastasis. These findings suggest that AHSG is a potential candidate for OC treatment.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 10","pages":"5365-5380"},"PeriodicalIF":1.5000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543047/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-789","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/29 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The primary cause of mortality in patients with ovarian cancer (OC) is tumor metastasis. A comprehensive understanding of the mechanisms underlying metastasis in OC is essential for accurate prognosis prediction and the development of targeted therapeutic agents. Our findings indicate that alpha-2 Heremans Schmid glycoprotein (AHSG) is downregulated in OC exosomes. Consequently, the objective of this study was to identify novel prognostic markers and potential therapeutic targets for OC.
Methods: Exosomes derived from OC cells and patient ascites were purified and applied to OC cells to assess their migratory ability using wound-healing and transwell assays. AHSG expression was enhanced by overexpressing lentivirus, and the resulting exosomes were isolated and co-cultured with OC cells to verify their effect on the migration ability of OC.
Results: Exosomes in ovarian malignant ascites have been demonstrated to promote OC metastasis. However, our findings indicate that AHSG is down-regulated in OC tissues and ascites exosomes. Furthermore, overexpression of AHSG in OC cells has been shown to markedly decrease their migratory ability, as well as reduce the migratory ability of cancer cells after co-culture of its exosomes with cancer cells.
Conclusions: The low expression of AHSG in exosomes derived from OC tissues and ascites is associated with metastatic progression in OC patients. Additionally, cancer-derived AHSG can be transported to OC cells via exosomes, where it inhibits OC migration in vitro and in vivo by regulating the p53/FAK/Src signaling pathway. The present study demonstrated that AHSG, derived from cancer cells, exerts a negative regulatory effect on OC cell motility, migration, and metastasis. These findings suggest that AHSG is a potential candidate for OC treatment.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
