Extracellular vesicles from tumor microenvironment transforms endothelial cell phenotype via downregulation of TRPV4 channels
Title
Extracellular vesicles from tumor microenvironment transforms endothelial cell phenotype via downregulation of TRPV4 channels
Creator
Guarino B;Adapala R;Kanugula A;Dougherty J;Paruchuri S;Mahmood K;Thodeti CK
Publisher
Faseb Journal
Date
2020
2020-04
Description
Angiogenesis, the formation of new blood vessels from existing ones, is a normal physiological process. However, deregulation of angiogenesis can lead to pathological states such as cancer, that is characterized by hyper‐permeable and tortuous vessels. We have recently shown a significant decrease in functional expression of the mechanosensitive ion channel, transient potential receptor vanilloid 4 (TRPV4), in tumor endothelial cells (TEC). Further, pharmacological activation of TRPV4 induced normalization of tumor vasculature and improved cancer therapy. However, the molecular mechanisms by which TRPV4 is downregulated in TEC is not yet known. To determine this mechanism, we focused on extracellular vesicles (EVs) derived from tumor cells. We first collected conditioned media (TCM) from tumor cells with and without pre‐treatment of an exosome inhibitor, GW4869. We found that treatment of human normal endothelial cells (hNEC) with TCM transformed them into tumor‐endothelial like (hTEC) phenotype as revealed by expression of TEM8, VEGFR2 membrane translocation, and abnormal tube formation. However, TCM from exosome inhibitor‐treated cells, failed to induce endothelial transformation. Further, we found that EVs isolated from TCM induced hNEC transformation to hTEC. Mechanistically, we found that tumor derived EVs induced functional downregulation of TRPV4 in hNEC as assessed by calcium imaging. Taken together, our results suggest that tumor derived EVs transforms normal endothelial cells via downregulation of TRPV4 channels.
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Format
journalArticle
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Issue
1
Volume
34
ISSN
0892-6638
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Department of Integrative Medical Sciences
Update Year & Number
September 2020 List
Citation
Guarino B;Adapala R;Kanugula A;Dougherty J;Paruchuri S;Mahmood K;Thodeti CK, “Extracellular vesicles from tumor microenvironment transforms endothelial cell phenotype via downregulation of TRPV4 channels,” NEOMED Bibliography Database, accessed April 26, 2024, https://neomed.omeka.net/items/show/11304.