Reihaneh Safavi-Sohi, Jeff Johnson, Yueying Liu, Jing Yang, Tyvette S Hilliard, Zhikun Wang, Christopher Barile, Josh Mijares, Ceming Wang, Hsueh-Chia Chang, Rebecca J Whelan, M Sharon Stack
{"title":"老年tumor-naïve宿主腹膜腔来源的细胞外小泡促进卵巢癌的粘附和侵袭。","authors":"Reihaneh Safavi-Sohi, Jeff Johnson, Yueying Liu, Jing Yang, Tyvette S Hilliard, Zhikun Wang, Christopher Barile, Josh Mijares, Ceming Wang, Hsueh-Chia Chang, Rebecca J Whelan, M Sharon Stack","doi":"10.1186/s12964-025-02273-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian cancer (OvCa) remains a leading cause of mortality among gynecological cancers. Metastasis to the peritoneum, characterized by tumor cell adhesion to and invasion of the mesothelial lining of the abdominal cavity, represents a critical early event in OvCa metastatic progression. The median age of diagnosis is 63 and there exists a strong correlation between advanced age, OvCa incidence and disease stage. Moreover, the aged peritoneal cavity represents a permissive niche for metastatic dissemination.</p><p><strong>Methods: </strong>To investigate age-related factors that influence host-tumor communication in metastatic progression, the current study isolated small extracellular vesicles (sEVs) from the peritoneal lavage of healthy tumor-naïve young (3-6 month) and aged (20-22 month) mice. sEVs were analyzed using LC-MS/MS to identify sEV protein cargoes and incubated with murine and human OvCa cells to evaluate effect on pro-metastatic behaviors.</p><p><strong>Results: </strong>Treatment of human or murine OvCa cells with sEVs from healthy aged hosts significantly enhanced adhesion to peritoneal mesothelial cells in a three-dimensional in vitro meso-mimetic culture assay and to the intact omentum in a short-term in vivo adhesion assay relative to OvCa cells treated with sEVs from young hosts. OvCa cell invasion of collagen gels was also enhanced by aged host-derived sEVs. Proteomic analysis of sEV protein cargos identified differentially expressed proteins in sEVs obtained from aged vs. young hosts that may play a significant role in regulation of adhesion. This was confirmed using meso-mimetic adhesion assays with function blocking antibodies or small molecule inhibitors, supporting a potential role for several proteins in promoting intra-peritoneal dissemination in the aged host.</p><p><strong>Conclusions: </strong>Results suggest that sEVs derived from the aged peritoneal microenvironment can contribute significantly to disease progression, highlighting sEV-mediated host: tumor communication as a potential therapeutic target for intervention in OvCa progression or recurrence in the aged host.</p>","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"308"},"PeriodicalIF":8.2000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211904/pdf/","citationCount":"0","resultStr":"{\"title\":\"Peritoneal cavity-derived small extracellular vesicles from aged tumor-naïve hosts promote ovarian cancer adhesion and invasion.\",\"authors\":\"Reihaneh Safavi-Sohi, Jeff Johnson, Yueying Liu, Jing Yang, Tyvette S Hilliard, Zhikun Wang, Christopher Barile, Josh Mijares, Ceming Wang, Hsueh-Chia Chang, Rebecca J Whelan, M Sharon Stack\",\"doi\":\"10.1186/s12964-025-02273-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Epithelial ovarian cancer (OvCa) remains a leading cause of mortality among gynecological cancers. Metastasis to the peritoneum, characterized by tumor cell adhesion to and invasion of the mesothelial lining of the abdominal cavity, represents a critical early event in OvCa metastatic progression. The median age of diagnosis is 63 and there exists a strong correlation between advanced age, OvCa incidence and disease stage. Moreover, the aged peritoneal cavity represents a permissive niche for metastatic dissemination.</p><p><strong>Methods: </strong>To investigate age-related factors that influence host-tumor communication in metastatic progression, the current study isolated small extracellular vesicles (sEVs) from the peritoneal lavage of healthy tumor-naïve young (3-6 month) and aged (20-22 month) mice. sEVs were analyzed using LC-MS/MS to identify sEV protein cargoes and incubated with murine and human OvCa cells to evaluate effect on pro-metastatic behaviors.</p><p><strong>Results: </strong>Treatment of human or murine OvCa cells with sEVs from healthy aged hosts significantly enhanced adhesion to peritoneal mesothelial cells in a three-dimensional in vitro meso-mimetic culture assay and to the intact omentum in a short-term in vivo adhesion assay relative to OvCa cells treated with sEVs from young hosts. OvCa cell invasion of collagen gels was also enhanced by aged host-derived sEVs. Proteomic analysis of sEV protein cargos identified differentially expressed proteins in sEVs obtained from aged vs. young hosts that may play a significant role in regulation of adhesion. This was confirmed using meso-mimetic adhesion assays with function blocking antibodies or small molecule inhibitors, supporting a potential role for several proteins in promoting intra-peritoneal dissemination in the aged host.</p><p><strong>Conclusions: </strong>Results suggest that sEVs derived from the aged peritoneal microenvironment can contribute significantly to disease progression, highlighting sEV-mediated host: tumor communication as a potential therapeutic target for intervention in OvCa progression or recurrence in the aged host.</p>\",\"PeriodicalId\":55268,\"journal\":{\"name\":\"Cell Communication and Signaling\",\"volume\":\"23 1\",\"pages\":\"308\"},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211904/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Communication and Signaling\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12964-025-02273-1\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12964-025-02273-1","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Peritoneal cavity-derived small extracellular vesicles from aged tumor-naïve hosts promote ovarian cancer adhesion and invasion.
Background: Epithelial ovarian cancer (OvCa) remains a leading cause of mortality among gynecological cancers. Metastasis to the peritoneum, characterized by tumor cell adhesion to and invasion of the mesothelial lining of the abdominal cavity, represents a critical early event in OvCa metastatic progression. The median age of diagnosis is 63 and there exists a strong correlation between advanced age, OvCa incidence and disease stage. Moreover, the aged peritoneal cavity represents a permissive niche for metastatic dissemination.
Methods: To investigate age-related factors that influence host-tumor communication in metastatic progression, the current study isolated small extracellular vesicles (sEVs) from the peritoneal lavage of healthy tumor-naïve young (3-6 month) and aged (20-22 month) mice. sEVs were analyzed using LC-MS/MS to identify sEV protein cargoes and incubated with murine and human OvCa cells to evaluate effect on pro-metastatic behaviors.
Results: Treatment of human or murine OvCa cells with sEVs from healthy aged hosts significantly enhanced adhesion to peritoneal mesothelial cells in a three-dimensional in vitro meso-mimetic culture assay and to the intact omentum in a short-term in vivo adhesion assay relative to OvCa cells treated with sEVs from young hosts. OvCa cell invasion of collagen gels was also enhanced by aged host-derived sEVs. Proteomic analysis of sEV protein cargos identified differentially expressed proteins in sEVs obtained from aged vs. young hosts that may play a significant role in regulation of adhesion. This was confirmed using meso-mimetic adhesion assays with function blocking antibodies or small molecule inhibitors, supporting a potential role for several proteins in promoting intra-peritoneal dissemination in the aged host.
Conclusions: Results suggest that sEVs derived from the aged peritoneal microenvironment can contribute significantly to disease progression, highlighting sEV-mediated host: tumor communication as a potential therapeutic target for intervention in OvCa progression or recurrence in the aged host.
期刊介绍:
Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior.
Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.