Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling

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

Genes and Diseases (Mar 2025)

Peritoneal adipose stem cell-derived extracellular vesicles mediate the regulation of ovarian cancer cell proliferation and migration through EGFR-NF-κB signaling

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

Affiliations

Lian Wang: Department 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.
Ning Luo: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Jihui Zhu: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Zubaidan Sulaiman: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Wenhan Yang: 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
Ke Hu: 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
Guihai Ai: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Weihong Yang: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Xiaowen Shao: Department of Gynecology and Obstetrics, Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Shengkai Jin: 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
Xue Zhang: Department 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
Yantao Fan: Department of Anesthesiology, Shanghai Gongli Hospital, Naval Military Medical University, Shanghai 200135, China
Dan Deng: Department 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.
Zhongping Cheng: 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.
Zhengliang Gao: 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.

Journal volume & issue: Vol. 12, no. 2
p. 101283

Abstract

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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.

Published in Genes and Diseases

ISSN: 2352-3042 (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Medicine: Medicine (General); Science: Biology (General): Genetics
Website: https://www.keaipublishing.com/en/journals/genes-and-diseases/

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