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Aquaporins and cell migration

  • M. C. Papadopoulos
  • S. Saadoun
  • A. S. VerkmanEmail author
Invited Review

Abstract

Aquaporin (AQP) water channels are expressed primarily in cell plasma membranes. In this paper, we review recent evidence that AQPs facilitate cell migration. AQP-dependent cell migration has been found in a variety of cell types in vitro and in mice in vivo. AQP1 deletion reduces endothelial cell migration, limiting tumor angiogenesis and growth. AQP4 deletion slows the migration of reactive astrocytes, impairing glial scarring after brain stab injury. AQP1-expressing tumor cells have enhanced metastatic potential and local infiltration. Impaired cell migration has also been seen in AQP1-deficient proximal tubule epithelial cells, and AQP3-deficient corneal epithelial cells, enterocytes, and skin keratinocytes. The mechanisms by which AQPs enhance cell migration are under investigation. We propose that, as a consequence of actin polymerization/depolymerization and transmembrane ionic fluxes, the cytoplasm adjacent to the leading edge of migrating cells undergoes rapid changes in osmolality. AQPs could thus facilitate osmotic water flow across the plasma membrane in cell protrusions that form during migration. AQP-dependent cell migration has potentially broad implications in angiogenesis, tumor metastasis, wound healing, glial scarring, and other events requiring rapid, directed cell movement. AQP inhibitors may thus have therapeutic potential in modulating these events, such as slowing tumor growth and spread, and reducing glial scarring after injury to allow neuronal regeneration.

Keywords

Angiogenesis AQP Astrocyte Cancer Cell membrane Cell motility Lamellipodium Water channel 

Notes

Acknowledgments

Supported by grants EB00415, DK35124, EY13574, HL59198, DK72517, and HL73856 from the National Institutes of Health, and Research Development Program and Drug Discovery grants from the Cystic Fibrosis Foundation (to ASV), and by a Wellcome Trust Clinician-Scientist Fellowship (to MCP).

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. C. Papadopoulos
    • 1
    • 2
  • S. Saadoun
    • 1
    • 2
  • A. S. Verkman
    • 1
    • 3
    Email author
  1. 1.Department of Medicine and PhysiologyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Academic Neurosurgery UnitSt. George’s, University of LondonLondonUK
  3. 3.University of California at San FranciscoSan FranciscoUSA

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