Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.

Title

Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.

Creator

Kanugula AK; Adapala RK; Jamaiyar A; Lenkey N; Guarino BD; Liedtke W; Yin L; Paruchuri S; Thodeti CK

Publisher

Angiogenesis

Date

2021
2021-03-03

Description

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.

Subject

Endothelial cell; Metastasis; Transient receptor potential vanilloid 4; Tumor angiogenesis; Vascular endothelial growth factor receptor 2

Format

journalArticle

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

ISSN

1573-7209 0969-6970

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences
NEOMED Postdoc Publications
NEOMED Student Publications

Update Year & Number

March 2021 List

Citation

Kanugula AK; Adapala RK; Jamaiyar A; Lenkey N; Guarino BD; Liedtke W; Yin L; Paruchuri S; Thodeti CK, “Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.,” NEOMED Bibliography Database, accessed May 26, 2022, https://neomed.omeka.net/items/show/11609.

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