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03.03.2021 | Original Paper

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

verfasst von: Anantha K. Kanugula, Ravi K. Adapala, Anurag Jamaiyar, Nina Lenkey, Brianna D. Guarino, Wolfgang Liedtke, Liya Yin, Sailaja Paruchuri, Charles K. Thodeti

Erschienen in: Angiogenesis | Ausgabe 3/2021

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Abstract

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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Titel: Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity
verfasst von: Anantha K. Kanugula
Ravi K. Adapala
Anurag Jamaiyar
Nina Lenkey
Brianna D. Guarino
Wolfgang Liedtke
Liya Yin
Sailaja Paruchuri
Charles K. Thodeti
Publikationsdatum: 03.03.2021
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 3/2021
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-021-09775-9

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