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Background <p>Epithelial ovarian cancer (EOC) frequently metastasizes to the omentum, yet the mechanisms driving this site-specific dissemination remain incompletely understood. Through transcriptomic profiling, we previously identified ADAMTS2 (A disintegrin and metalloproteinase with thrombospondin type 1 motifs 2) as the most upregulated gene in highly metastatic EOC (EOC-HM) cells. Here, we investigated the functional role of ADAMTS2 in orchestrating the omental metastatic niche.</p> Results <p>In orthotopic mouse models, silencing ADAMTS2 in EOC-HM cells significantly suppressed spontaneous intraperitoneal metastasis and extended survival. Mechanistically, we observed a negative correlation between tumoral ADAMTS2 expression and omental collagen deposition in both murine models and patient samples, as visualized by polarized picrosirius red staining. Furthermore, EOC-HM cells secreted elevated levels of ADAMTS2 compared to parental lines, and intraperitoneal injection of this ADAMTS2-rich supernatant was sufficient to reduce omental collagen density in vivo. In vitro assays confirmed that ADAMTS2 knockdown impaired the invasive capacity of EOC cells through collagen I matrices and diminished the collagenolytic activity of their conditioned media.</p> Conclusions <p>These findings identify tumor-derived ADAMTS2 as a key initiator of extracellular matrix remodeling in the omentum that facilitates subsequent metastatic colonization, providing mechanistic insight into premetastatic niche formation and suggesting ADAMTS2 as a potential therapeutic target in EOC.</p>

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Ovarian cancer-derived ADAMTS2 promotes the omental pre-metastatic niche formation through remodeling collagen I

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Jing Guo,
  • Xinyi Wu,
  • Qiulei Wu,
  • Lin Huang,
  • Wenhan Li,
  • Yan Wei,
  • Le Chen,
  • Feiquan Ying

摘要

Background

Epithelial ovarian cancer (EOC) frequently metastasizes to the omentum, yet the mechanisms driving this site-specific dissemination remain incompletely understood. Through transcriptomic profiling, we previously identified ADAMTS2 (A disintegrin and metalloproteinase with thrombospondin type 1 motifs 2) as the most upregulated gene in highly metastatic EOC (EOC-HM) cells. Here, we investigated the functional role of ADAMTS2 in orchestrating the omental metastatic niche.

Results

In orthotopic mouse models, silencing ADAMTS2 in EOC-HM cells significantly suppressed spontaneous intraperitoneal metastasis and extended survival. Mechanistically, we observed a negative correlation between tumoral ADAMTS2 expression and omental collagen deposition in both murine models and patient samples, as visualized by polarized picrosirius red staining. Furthermore, EOC-HM cells secreted elevated levels of ADAMTS2 compared to parental lines, and intraperitoneal injection of this ADAMTS2-rich supernatant was sufficient to reduce omental collagen density in vivo. In vitro assays confirmed that ADAMTS2 knockdown impaired the invasive capacity of EOC cells through collagen I matrices and diminished the collagenolytic activity of their conditioned media.

Conclusions

These findings identify tumor-derived ADAMTS2 as a key initiator of extracellular matrix remodeling in the omentum that facilitates subsequent metastatic colonization, providing mechanistic insight into premetastatic niche formation and suggesting ADAMTS2 as a potential therapeutic target in EOC.