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

Publication ,  Journal Article
Kanugula, AK; Adapala, RK; Jamaiyar, A; Lenkey, N; Guarino, BD; Liedtke, W; Yin, L; Paruchuri, S; Thodeti, CK
Published in: Angiogenesis
August 2021

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 (TRPV4ECKO) mice by crossing TRPV4lox/lox mice with Tie2-Cre mice. Tumor growth and metastasis were significantly increased in a syngeneic Lewis lung carcinoma tumor model of TRPV4ECKO mice compared to TRPV4lox/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 TRPV4ECKO 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.

Duke Scholars

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Published In

Angiogenesis

DOI

EISSN

1573-7209

Publication Date

August 2021

Volume

24

Issue

3

Start / End Page

647 / 656

Location

Germany

Related Subject Headings

  • TRPV Cation Channels
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mice, Knockout
  • Mice
  • Gene Expression Regulation, Neoplastic
  • Carcinoma, Lewis Lung
  • Animals
 

Citation

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Kanugula, A. K., Adapala, R. K., Jamaiyar, A., Lenkey, N., Guarino, B. D., Liedtke, W., … Thodeti, C. K. (2021). Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity. Angiogenesis, 24(3), 647–656. https://doi.org/10.1007/s10456-021-09775-9
Kanugula, Anantha K., Ravi K. Adapala, Anurag Jamaiyar, Nina Lenkey, Brianna D. Guarino, Wolfgang Liedtke, Liya Yin, Sailaja Paruchuri, and Charles K. Thodeti. “Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.Angiogenesis 24, no. 3 (August 2021): 647–56. https://doi.org/10.1007/s10456-021-09775-9.
Kanugula AK, Adapala RK, Jamaiyar A, Lenkey N, Guarino BD, Liedtke W, et al. Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity. Angiogenesis. 2021 Aug;24(3):647–56.
Kanugula, Anantha K., et al. “Endothelial TRPV4 channels prevent tumor growth and metastasis via modulation of tumor angiogenesis and vascular integrity.Angiogenesis, vol. 24, no. 3, Aug. 2021, pp. 647–56. Pubmed, doi:10.1007/s10456-021-09775-9.
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. Angiogenesis. 2021 Aug;24(3):647–656.
Journal cover image

Published In

Angiogenesis

DOI

EISSN

1573-7209

Publication Date

August 2021

Volume

24

Issue

3

Start / End Page

647 / 656

Location

Germany

Related Subject Headings

  • TRPV Cation Channels
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mice, Knockout
  • Mice
  • Gene Expression Regulation, Neoplastic
  • Carcinoma, Lewis Lung
  • Animals