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Text
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<a href="http://doi.org/10.1007/s10456-021-09775-9" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s10456-021-09775-9</a>
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ISSN
1573-7209 0969-6970
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Update Year & Number
March 2021 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Integrative Medical Sciences
NEOMED Postdoc Publications
NEOMED Student Publications
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Title
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Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.
Publisher
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Angiogenesis
Date
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2021
2021-03-03
Subject
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Endothelial cell; Metastasis; Transient receptor potential vanilloid 4; Tumor angiogenesis; Vascular endothelial growth factor receptor 2
Creator
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Kanugula AK; Adapala RK; Jamaiyar A; Lenkey N; Guarino BD; Liedtke W; Yin L; Paruchuri S; Thodeti CK
Description
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Transient receptor potential vanilloid 4 (TRPV4) is a ubiquitously expressed polymodally activated ion channel. TRPV4 has been implicated in tumor progression; however, the cell-specific role of TRPV4 in tumor growth, angiogenesis, and metastasis is unknown. Here, we generated endothelial-specific TRPV4 knockout (TRPV4(ECKO)) mice by crossing TRPV4(lox/lox) mice with Tie2-Cre mice. Tumor growth and metastasis were significantly increased in a syngeneic Lewis lung carcinoma tumor model of TRPV4(ECKO) mice compared to TRPV4(l)(ox/lox) mice. Multiphoton microscopy, dextran leakage, and immunohistochemical analysis revealed increased tumor angiogenesis and metastasis that were correlated with aberrant leaky vessels (increased width and reduced pericyte and VE-cadherin coverage). Mechanistically, increases in VEGFR2, p-ERK, and MMP-9 expression and DQ gelatinase activity were observed in the TRPV4(ECKO) mouse tumors. Our results demonstrated that endothelial TRPV4 is a critical modulator of vascular integrity and tumor angiogenesis and that deletion of TRPV4 promotes tumor angiogenesis, growth, and metastasis.
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<a href="http://doi.org/10.1007/s10456-021-09775-9" target="_blank" rel="noreferrer noopener">10.1007/s10456-021-09775-9</a>
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journalArticle
2021
Adapala RK
angiogenesis
Department of Integrative Medical Sciences
endothelial cell
Guarino BD
Jamaiyar A
journalArticle
Kanugula AK
Lenkey N
Liedtke W
March 2021 List
Metastasis
NEOMED College of Medicine
NEOMED Postdoc Publications
NEOMED Student Publications
Paruchuri S
Thodeti CK
Transient receptor potential vanilloid 4
tumor angiogenesis
Vascular endothelial growth factor receptor 2
Yin L