Cysteinyl Leukotriene 2 Receptor Enhances Angiogenesis, Vascular Permeability And Tumor Metastasis
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Duah E; Kondeti V; Al-Azzam N; Adapala R; Patil P; Thodeti C; Paruchuri S
Faseb Journal
2016
2016-04
Journal Article or Conference Abstract Publication
n/a
Extracellular vesicles from tumor microenvironment transforms endothelial cell phenotype via downregulation of TRPV4 channels
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.
Guarino B;Adapala R;Kanugula A;Dougherty J;Paruchuri S;Mahmood K;Thodeti CK
Faseb Journal
2020
2020-04
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journalArticle
<a href="http://doi.org/10.1096/fasebj.2020.34.s1.05946" target="_blank" rel="noreferrer noopener">10.1096/fasebj.2020.34.s1.05946</a>
Mechanosensitive Trpv4 Channels Mediate Cardiac Myofibroblast Differentitation
Cardiovascular System & Cardiology; Extracellular matrix; fibrosis; Ion channels; Myocardial infarction; Signal transduction
Adapala R; Luther D; Shah S; Meszaros J G; Chilian W M; Thodeti C K
Circulation
2011
2011-11
Journal Article or Conference Abstract Publication
n/a
Targetting Cysteinyl Leukotriene 2 Receptor as a Therapeutic Target for Tumor Growth and Metastasis: A New Function for an Old Receptor
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Teegala L R; Duah E; Kondeti V; Al-Azzam N Z; Adapala R; Ghebreigziabher S; Thodeti C; Paruchuri S
Faseb Journal
2017
2017-04
Journal Article
n/a
TRPV4 Channels Modulate Pathological Angiogenesis via Rho/Rho Kinase Pathway
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Cappelli H; Thoppil R; Adapala R; Paruchuri S; Meszaros J; Thodeti C
Faseb Journal
2015
2015-04
Journal Article or Conference Abstract Publication
n/a
TRPV4 Channels Regulate Tumor Angiogenesis via Modulation of ERK1/2-DependentTumor Endothelial Cell Proliferation
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Thoppil R; Adapala R; Cappelli H; Paruchuri S; Meszaros J G; Thodeti C
Faseb Journal
2015
2015-04
Journal Article
n/a