Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption

Samira Saadoun, Marios C. Papadopoulos, Mariko Chikuma, A. S. Verkman

Research output: Contribution to journalArticle

556 Citations (Scopus)

Abstract

Aquaporin-1 (AQP1) is a water channel protein expressed widely in vascular endothelia, where it increases cell membrane water permeability. The role of AQP1 in endothelial cell function is unknown.Here we show remarkably impaired tumour growth in AQP1-null mice after subcutaneous or intracranial tumour cell implantation, with reduced tumour vascularity and extensive necrosis. A new mechanism for the impaired angiogenesis was established from cell culture studies. Although adhesion and proliferation were similar in primary cultures of aortic endothelia from wild-type and from AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells, with abnormal vessel formation in vitro. Stable transfection of non-endothelial cells with AQP1 or with a structurally different water-selective trans porter (AQP4) accelerated cell migration and wound healing in vitro.Motile AQP1-expressing cells had prominent membrane ruffles at the leading edge with polarization of AQP1 protein to lamellipodia, where rapid water fluxes occur. Our findings support a fundamental role of water channels in cell migration, which is central to diverse biological phenomena including angiogenesis, wound healing, tumour spread and organ regeneration.

Original languageEnglish
Pages (from-to)786-792
Number of pages7
JournalNature
Volume434
Issue number7034
DOIs
Publication statusPublished - 2005 Apr 7
Externally publishedYes

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Aquaporin 1
Cell Movement
Genes
Aquaporins
Wound Healing
Water
Neoplasms
Cell Membrane Permeability
Biological Phenomena
Null Lymphocytes
Pseudopodia
Vascular Endothelium
Endothelium
Transfection
Regeneration
Necrosis
Endothelial Cells
Cell Culture Techniques
Membranes

ASJC Scopus subject areas

  • General

Cite this

Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. / Saadoun, Samira; Papadopoulos, Marios C.; Chikuma, Mariko; Verkman, A. S.

In: Nature, Vol. 434, No. 7034, 07.04.2005, p. 786-792.

Research output: Contribution to journalArticle

Saadoun, Samira ; Papadopoulos, Marios C. ; Chikuma, Mariko ; Verkman, A. S. / Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. In: Nature. 2005 ; Vol. 434, No. 7034. pp. 786-792.
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