Journal ArticleDOI
Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption
TLDR
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, is supported.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 transporter (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.read more
Citations
More filters
Journal ArticleDOI
Dysregulated pH: a perfect storm for cancer progression.
TL;DR: The central role of pH sensors in cancer cell adaptations is highlighted and how dysregulated pH could be exploited to develop cancer-specific therapeutics is suggested.
Journal ArticleDOI
Plant Aquaporins: Membrane Channels with Multiple Integrated Functions
TL;DR: How a wide range of selectivity profiles and regulation properties allows aquaporins to be integrated in numerous functions, throughout plant development, and during adaptations to variable living conditions is examined.
Journal ArticleDOI
Stem Cell–Related “Self-Renewal” Signature and High Epidermal Growth Factor Receptor Expression Associated With Resistance to Concomitant Chemoradiotherapy in Glioblastoma
Anastasia Murat,Eugenia Migliavacca,Thierry Gorlia,Wanyu L. Lambiv,Tal Shay,Marie-France Hamou,Nicolas de Tribolet,Luca Regli,Wolfgang Wick,Mathilde C.M. Kouwenhoven,Johannes A. Hainfellner,Frank L. Heppner,Pierre-Yves Dietrich,Yitzhak Zimmer,J. Gregory Cairncross,Robert-Charles Janzer,Eytan Domany,Mauro Delorenzi,Roger Stupp,Monika E. Hegi +19 more
TL;DR: This study provides first clinical evidence for the implication of a "glioma stem cell" or "self-renewal" phenotype in treatment resistance of glioblastoma.
Journal ArticleDOI
Aquaporin water channels in the nervous system
TL;DR: The aquaporins (AQPs) are plasma membrane water-transporting proteins that are expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation, and are potential drug targets for several neurological conditions.
Journal ArticleDOI
More than just water channels: unexpected cellular roles of aquaporins.
TL;DR: Aquaporins facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells.
References
More filters
Journal ArticleDOI
Cell Migration: A Physically Integrated Molecular Process
TL;DR: The authors are grateful for financial support from the National Institutes of Health (grants GM23244 and GM53905), and to very helpful comments on the manuscript from Elliot Elson, Vlodya Gelfand, Paul Matsudaira, Julie Theriot, and Sally Zigmond.
Journal ArticleDOI
Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia
TL;DR: The aquaporin CHIP (channel-forming integral membrane protein of 28 kDa), a molecular water channel, is abundant in erythrocytes and water-permeable segments of the nephron as mentioned in this paper.
Journal ArticleDOI
Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema
TL;DR: Aquaporin‐4‐mediated transcellular water movement is crucial for fluid clearance in vasogenic brain edema, suggesting AQP4 activation and/or up‐regulation as a novel therapeutic option in vasgenic brain edma.
Journal ArticleDOI
Intramyocardial Transplantation of Autologous Endothelial Progenitor Cells for Therapeutic Neovascularization of Myocardial Ischemia
Atsuhiko Kawamoto,Tengis Tkebuchava,Jun Ichi Yamaguchi,Hiromi Nishimura,Young Sup Yoon,Charles E. Milliken,Shigeki Uchida,Osamu Masuo,Hideki Iwaguro,Hong Ma,Allison Hanley,Marcy Silver,Marianne Kearney,Douglas W. Losordo,Jeffrey M. Isner,Takayuki Asahara +15 more
TL;DR: In this article, the authors investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia.
Journal ArticleDOI
Severely Impaired Urinary Concentrating Ability in Transgenic Mice Lacking Aquaporin-1 Water Channels
Tonghui Ma,Baoxue Yang,Annemarie Gillespie,Elaine J. Carlson,Charles J. Epstein,Alan S. Verkman +5 more
TL;DR: The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication, and AQP 1 is thus required for the formation of a concentrated urine by the kidney.