Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling
Peritoneal dissemination frequently develops in patients with ovarian cancer (OC) and is associated with recurrence and metastasis. However, the cellular components and mechanisms supporting OC peritoneal metastasis are poorly understood. To elucidate these, we utilized RNA sequencing to investigate...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-03-01
|
| Series: | Genes and Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304224000801 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850120059834335232 |
|---|---|
| author | Lian Wang Ning Luo Jihui Zhu Zubaidan Sulaiman Wenhan Yang Ke Hu Guihai Ai Weihong Yang Xiaowen Shao Shengkai Jin Xue Zhang Yantao Fan Dan Deng Zhongping Cheng Zhengliang Gao |
| author_facet | Lian Wang Ning Luo Jihui Zhu Zubaidan Sulaiman Wenhan Yang Ke Hu Guihai Ai Weihong Yang Xiaowen Shao Shengkai Jin Xue Zhang Yantao Fan Dan Deng Zhongping Cheng Zhengliang Gao |
| author_sort | Lian Wang |
| collection | DOAJ |
| description | Peritoneal dissemination frequently develops in patients with ovarian cancer (OC) and is associated with recurrence and metastasis. However, the cellular components and mechanisms supporting OC peritoneal metastasis are poorly understood. To elucidate these, we utilized RNA sequencing to investigate the cellular composition and function. Insights from transcriptome analyses suggested that OC cells from malignant ascites persisted in a quiescent state of low metabolic activity and after metastases to the peritoneum, arrested OC cells were reactivated and induced back to the cell cycle, suggesting that the peritoneum served as a favor tumor microenvironment. To elucidate the mechanisms, we then developed long-range migration and competitive inhibition assays and showed that peritoneal adipose-derived stem cells-derived extracellular vesicles (ADSCs-EVs) mediated preferential migration of OC cells toward peritoneal ADSCs but not other representative cells from the peritoneal cavity. In line with phenotypic changes, transcriptomic analysis revealed that patient peritoneal ADSCs-EVs stimulated the expression of numerous genes associated with OC cell proliferation and migration; among them, the epidermal growth factor receptor (EGFR) and nuclear factor kappa B (NF-κB) signaling pathways were highly enriched. We also found that peritoneal ADSCs produced and secreted key EGFR signaling molecules, including EGF and EGFR, into ADSCs-EVs. Upon fusion with OC cells, ADSCs-EVs up-regulated the EGFR-NF-κB axis and promoted OC cell proliferation and migration. Interference with either ADSCs-EVs production or EGFR signaling abolished the proliferation and migration effect. The results show that ADSCs modulate OC cell proliferation and migration at multiple layers, constituting a key mechanism in OC progression. |
| format | Article |
| id | doaj-art-cd4094a879fc4e938dca7a3f3b755476 |
| institution | OA Journals |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-cd4094a879fc4e938dca7a3f3b7554762025-08-20T02:35:29ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-03-0112210128310.1016/j.gendis.2024.101283Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signalingLian Wang0Ning Luo1Jihui Zhu2Zubaidan Sulaiman3Wenhan Yang4Ke Hu5Guihai Ai6Weihong Yang7Xiaowen Shao8Shengkai Jin9Xue Zhang10Yantao Fan11Dan Deng12Zhongping Cheng13Zhengliang Gao14Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China; Shanghai Engineering Research Center of Organ Repair, Shanghai University School of Medicine, Shanghai 200444, China; Corresponding author. Shanghai Tenth People's Hospital, No. 301, Yanchang Middle Road, Jingan District, Shanghai 200072, China.Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China; Shanghai Engineering Research Center of Organ Repair, Shanghai University School of Medicine, Shanghai 200444, China; Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University School of Medicine, Nantong, Jiangsu 216002, ChinaDepartment of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China; Shanghai Engineering Research Center of Organ Repair, Shanghai University School of Medicine, Shanghai 200444, China; Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University School of Medicine, Nantong, Jiangsu 216002, ChinaDepartment of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China; Shanghai Engineering Research Center of Organ Repair, Shanghai University School of Medicine, Shanghai 200444, China; Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University School of Medicine, Nantong, Jiangsu 216002, ChinaDepartment of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, ChinaDepartment of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, ChinaDepartment of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Corresponding author. Shanghai Children's Medical Center, No. 1678 Dongfang Road, Pudong New District, Shanghai 200127, China.Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author. Shanghai Tenth People's Hospital, No. 301, Yanchang Middle Road, Jingan District, Shanghai 200072, China.Department of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China; Shanghai Engineering Research Center of Organ Repair, Shanghai University School of Medicine, Shanghai 200444, China; Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Shanghai University School of Medicine, Nantong, Jiangsu 216002, China; China-Japan Friendship Medical Research Institute, School of Medicine, Shanghai University, Shanghai 200444, China; Corresponding author. Shanghai Gongli Hospital, No. 219 Miaopu Road, Pudong New District, Shanghai 200135, China.Peritoneal dissemination frequently develops in patients with ovarian cancer (OC) and is associated with recurrence and metastasis. However, the cellular components and mechanisms supporting OC peritoneal metastasis are poorly understood. To elucidate these, we utilized RNA sequencing to investigate the cellular composition and function. Insights from transcriptome analyses suggested that OC cells from malignant ascites persisted in a quiescent state of low metabolic activity and after metastases to the peritoneum, arrested OC cells were reactivated and induced back to the cell cycle, suggesting that the peritoneum served as a favor tumor microenvironment. To elucidate the mechanisms, we then developed long-range migration and competitive inhibition assays and showed that peritoneal adipose-derived stem cells-derived extracellular vesicles (ADSCs-EVs) mediated preferential migration of OC cells toward peritoneal ADSCs but not other representative cells from the peritoneal cavity. In line with phenotypic changes, transcriptomic analysis revealed that patient peritoneal ADSCs-EVs stimulated the expression of numerous genes associated with OC cell proliferation and migration; among them, the epidermal growth factor receptor (EGFR) and nuclear factor kappa B (NF-κB) signaling pathways were highly enriched. We also found that peritoneal ADSCs produced and secreted key EGFR signaling molecules, including EGF and EGFR, into ADSCs-EVs. Upon fusion with OC cells, ADSCs-EVs up-regulated the EGFR-NF-κB axis and promoted OC cell proliferation and migration. Interference with either ADSCs-EVs production or EGFR signaling abolished the proliferation and migration effect. The results show that ADSCs modulate OC cell proliferation and migration at multiple layers, constituting a key mechanism in OC progression.http://www.sciencedirect.com/science/article/pii/S2352304224000801Adipose-derived stem cellsEGFR/NK-κB axisExtracellular vesiclesMetastasisOvarian cancer |
| spellingShingle | Lian Wang Ning Luo Jihui Zhu Zubaidan Sulaiman Wenhan Yang Ke Hu Guihai Ai Weihong Yang Xiaowen Shao Shengkai Jin Xue Zhang Yantao Fan Dan Deng Zhongping Cheng Zhengliang Gao Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling Genes and Diseases Adipose-derived stem cells EGFR/NK-κB axis Extracellular vesicles Metastasis Ovarian cancer |
| title | Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling |
| title_full | Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling |
| title_fullStr | Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling |
| title_full_unstemmed | Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling |
| title_short | Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling |
| title_sort | peritoneal adipose stem cell derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through egfr nf κb signaling |
| topic | Adipose-derived stem cells EGFR/NK-κB axis Extracellular vesicles Metastasis Ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2352304224000801 |
| work_keys_str_mv | AT lianwang peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT ningluo peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT jihuizhu peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT zubaidansulaiman peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT wenhanyang peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT kehu peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT guihaiai peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT weihongyang peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT xiaowenshao peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT shengkaijin peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT xuezhang peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT yantaofan peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT dandeng peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT zhongpingcheng peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling AT zhenglianggao peritonealadiposestemcellderivedextracellularvesiclesmediatetheregulationofovariancancercellproliferationandmigrationthroughegfrnfkbsignaling |