Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis

• DOI: 10.1073/pnas.1920037117
• Publication Date: 2020-10-02T00:10:54Z
• Authors: Wan-Ning Li; Kuei-Yang Hsiao; Chu-An Wang; Ning Chang; Pei-Ling Hsu; Chung-Hsien Sun; Shang-Rung Wu; Meng-Hsing Wu; Shaw-Jenq Tsai
• Keywords: Vascular Endothelial Growth Factor C; Endometriosis; Endothelial Cells; 3. Good health; COUP Transcription Factor II; Extracellular Vesicles; Mice; 03 medical and health sciences; 0302 clinical medicine; Immune System; Animals; Cytokines; Humans; Female; Lymphangiogenesis; Lymphatic Vessels

Significance Endometriosis is a highly prevalent proinflammatory disease without reliable diagnostic biomarkers and cannot be cured by nowadays’ medical treatments. Herein, we identified that extracellular vesicle (EV)-associated VEGF-C, secreted by proinflammatory cytokine-stimulated endometriotic stromal cells, is a critical modulator for endometriosis progression by promoting lymphangiogenesis. Invaded lymphatic vessels may serve as a canal for the infiltration of immune cells, which further enhances the inflammatory status in the endometriotic microenvironment and produces more EV-VEGF-C. The elevated circulating EV-VEGF-C is a sensitive and reliable biomarker for detecting endometriosis. These data advance our understanding of the pathophysiology of endometriosis and suggest VEGF-C can be a noninvasive diagnostic biomarker and a potential therapeutic target for endometriosis.