Open AccessExtracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis
Author(s) -
Wan-Ning Li,
KueiYang Hsiao,
Chu-An Wang,
Ning Chang,
PeiLing Hsu,
Chung-Hsien Sun,
Shang-Rung Wu,
MengHsing Wu,
ShawJenq Tsai
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1920037117
Subject(s) - endometriosis , proinflammatory cytokine , lymphangiogenesis , stromal cell , lymphatic system , immune system , cancer research , medicine , biomarker , infiltration (hvac) , tumor microenvironment , chemokine , inflammation , pathology , immunology , biology , cancer , metastasis , biochemistry , physics , thermodynamics
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.
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