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Background <p>Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with tumor microenvironment playing a critical role in its progression. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication within the tumor microenvironment, but their contribution to ovarian cancer progression through macrophage regulation remains poorly understood.</p> Methods <p>EVs were isolated from ovarian cancer cell lines (SKOV3, HO8910, and ID8) by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. The polarization of THP-1 macrophages and bone marrow-derived macrophages (BMDMs) was assessed after co-culture with cancer cells or treatment with cancer cell-derived EVs. Tube formation assays, cell proliferation, and VEGFR expression in human umbilical vein endothelial cells (HUVECs) were evaluated. In vivo, nude mice bearing SKOV3 tumors were treated with ovarian cancer-derived EVs, and tumor growth, macrophage infiltration, and angiogenesis were analyzed.</p> Results <p>Ovarian cancer patients exhibited significantly increased M2-like monocytes proportions in both peripheral blood and tumor tissues compared to non-cancer controls (<i>p</i> &lt; 0.05). CD31 expression was also elevated in ovarian cancer tissues and correlated with poor prognosis. In vitro, ovarian cancer cells promoted M2 polarization of macrophages (<i>p</i> &lt; 0.001). EVs derived from ovarian cancer cells were successfully isolated, characterized, and shown to be internalized by macrophages. These cancer-derived EVs induced M2 polarization of macrophages (<i>p</i> &lt; 0.0001) and enhanced the tube formation ability of HUVECs through upregulation of VEGFR expression. In the mouse model, ovarian cancer-derived EVs significantly promoted tumor growth (<i>p</i> &lt; 0.0001), increased M2 macrophage infiltration, and enhanced CD31 expression compared to control groups.</p> Conclusions <p>Our findings demonstrate that ovarian cancer-derived EVs promote tumor progression by inducing M2 macrophage polarization and enhancing angiogenesis. This study not only elucidates a novel mechanism by which ovarian cancer cells interact with the tumor microenvironment but also suggests that targeting cancer-derived EVs could be a promising therapeutic strategy for ovarian cancer treatment.</p>

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Extracellular vesicles derived from ovarian cancer cells promote tumor progression through m2 macrophage polarization and enhanced angiogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月24日

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  • Yi Zhang,
  • Tiantian Dai,
  • Dandan Chu,
  • Wei Zhang,
  • Xujie Wang,
  • Jinhua Zhou

摘要

Background

Ovarian cancer is one of the most lethal gynecologic malignancies worldwide, with tumor microenvironment playing a critical role in its progression. Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication within the tumor microenvironment, but their contribution to ovarian cancer progression through macrophage regulation remains poorly understood.

Methods

EVs were isolated from ovarian cancer cell lines (SKOV3, HO8910, and ID8) by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. The polarization of THP-1 macrophages and bone marrow-derived macrophages (BMDMs) was assessed after co-culture with cancer cells or treatment with cancer cell-derived EVs. Tube formation assays, cell proliferation, and VEGFR expression in human umbilical vein endothelial cells (HUVECs) were evaluated. In vivo, nude mice bearing SKOV3 tumors were treated with ovarian cancer-derived EVs, and tumor growth, macrophage infiltration, and angiogenesis were analyzed.

Results

Ovarian cancer patients exhibited significantly increased M2-like monocytes proportions in both peripheral blood and tumor tissues compared to non-cancer controls (p < 0.05). CD31 expression was also elevated in ovarian cancer tissues and correlated with poor prognosis. In vitro, ovarian cancer cells promoted M2 polarization of macrophages (p < 0.001). EVs derived from ovarian cancer cells were successfully isolated, characterized, and shown to be internalized by macrophages. These cancer-derived EVs induced M2 polarization of macrophages (p < 0.0001) and enhanced the tube formation ability of HUVECs through upregulation of VEGFR expression. In the mouse model, ovarian cancer-derived EVs significantly promoted tumor growth (p < 0.0001), increased M2 macrophage infiltration, and enhanced CD31 expression compared to control groups.

Conclusions

Our findings demonstrate that ovarian cancer-derived EVs promote tumor progression by inducing M2 macrophage polarization and enhancing angiogenesis. This study not only elucidates a novel mechanism by which ovarian cancer cells interact with the tumor microenvironment but also suggests that targeting cancer-derived EVs could be a promising therapeutic strategy for ovarian cancer treatment.