Hematogenous Metastasis of Ovarian Cancer: Rethinking Mode of Spread

• Epithelial ovarian cancer metastasizes to the omentum hematogenously
• Elevated levels of NRG1 in the omentum promote the homing of ovarian cancer cells
• ErbB3-expressing CTCs foster hematogenous metastases
• ErbB3 knockdown inhibits ovarian cancer metastasis

SummaryOvarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin 1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.

Graphical AbstractFigure optionsDownload high-quality image (248 K)Download as PowerPoint slide