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

NATURE 434, 786-792, 2005

Speaker：陳家如                         Time：13:10~14:00, May 11, 2005

Commentator：辛致煒                     Place：Room 601

Abstract:

Water channel proteins, aquaporins, are integral membrane proteins serving in the permeation of water and some other small molecules. Eleven isoforms of aquaporins have been identified from various tissues to date. They are expressed in tissue- and cell-specific manners¹. AQP1 protein is expressed strongly in proliferating microvessels in human and rat malignant brain tumours, bone marrow microvessels in human multiple myeloma, and proliferating microvessels in chick embryo chorioallantoic membrane. Increased aquaporin expression has also been observed in malignant tumour cells, indicating a possible role for water channels in tumour growth and spread. To prove the postulation, the authors implanted melanoma cells subcutaneously in wild type and AQP1-null mice. The tumor growth in AQP1-null mice is slow than wild type, and the microvessel formation is also reduced in AQP1-null mice. Then, they studied angiogenesis in AQP1-null mice by in vitro Matrigel assay. The Matrigel findinds confirm impaired angiogenesis in AQP1-null mice. Besides, the authors test whether the angiogenesis required for AQP1-expressing endothelial cells function. Endothelial cells were generated from mouse aorta and measured of cell proliferation, adhesion and migration. Although adhesion and proliferation were no difference between wild-type and AQP1-null mice, cell migration was greatly impaired in AQP1-deficient cells. Stable transfection of non-endothelial cells with AQP1 acclerated 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. The authors’ 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 regeneration².

References:

1. Toshiyuki Matsuzaki, Yuki Tajika, Nomingerel Tserentsoodol, Takeshi Suzuki, Takeo Aoki, Haruo Hagiwara and Kuniaki Takata  Aquaporins: a water channel family Anatomical Science International 77, 85–93, 2002

2. Samira Saadoun, Marios C. Papadopoulos, Mariko Hara-Chikuma & A. S. Verkman

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

  NATURE 434, 786-792, 2005