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

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

doi:10.1038/nature03460

Cited by 668 publications

(639 citation statements)

References 27 publications

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“…We discovered an interesting role of AQPs in cell migration, as originally demonstrated in endothelial cells and various transfected cells (Saadoun et al, 2005a), and subsequently in brain astroglial cells (Saadoun et al, 2005b, Auguste et al, 2007, kidney proximal tubule cells (Hara-Chikuma and Verkman, 2006), skin cells (Hara-Chikuma and Verkman, 2008b) and tumor cells (Hu and Verkman, 2006). Fig.…”

Section: Aqp Roles Related To Aqp-facilitated Water Transportmentioning

confidence: 90%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

171

117

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The aquaporins (AQPs) are integral membrane proteins whose main function is to transport water across cell membranes in response to osmotic gradients. At the ocular surface, AQP1 is expressed in corneal endothelium, AQP3 and AQP5 in corneal epithelium, and AQP3 in conjunctival epithelium. AQPs are also expressed in lens fiber cells (AQP0), lens epithelium (AQP1), ciliary epithelium (AQP1, AQP4) and retinal Müller cells (AQP4). Mutations in AQP0 produce congenital cataracts in humans. Analysis of knockout mice lacking individual AQPs suggests their involvement in maintenance of corneal and lens transparency, corneal epithelial repair, intraocular pressure regulation, retinal signal transduction and retinal swelling following injury. The mouse phenotype findings implicate AQPs as potential drug targets for therapy of elevated intraocular pressure and ocular disorders involving the cornea, lens and retina. However, much research remains in defining cell-level mechanisms for the ocular AQP functions, in establishing the relevance to human eye disease of conclusions from knockout mice, and in developing AQPmodulating drugs.

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Section: Aqp Roles Related To Aqp-facilitated Water Transportmentioning

confidence: 90%

Functions of aquaporins in the eye

Verkman

Ruiz-Ederra

Levin

2008

Progress in Retinal and Eye Research

171

117

View full text Add to dashboard Cite

show abstract

“…Because of the noncompliant skull, brain tumor edema contributes to increased intracranial pressure, which reduces cerebral blood flow and produces brain herniation. Recent evidence for the involvement of AQPs in angiogenesis, and in tumor cell migration and proliferation [10][11][12][13][14], suggest new roles of AQPs in tumor biology, in addition to their potential role in tumor-associated edema.…”

Section: Aqp Expression In Tumorsmentioning

confidence: 99%

Aquaporins—new players in cancer biology

2008

Self Cite

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The aquaporins (AQPs) are small, integralmembrane proteins that selectively transport water across cell plasma membranes. A subset of AQPs, the aquaglyceroporins, also transport glycerol. AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors. Recent discoveries of AQP involvement in cell migration and proliferation suggest that AQPs play key roles in tumor biology. AQP1 is ubiquitously expressed in tumor vascular endothelium, and AQP1-null mice show defective tumor angiogenesis resulting from impaired endothelial cell migration. AQP-expressing cancer cells show enhanced migration in vitro and greater local tumor invasion, tumor cell extravasation, and metastases in vivo. AQP-dependent cell migration may involve AQP-facilitated water influx into lamellipodia at the front edge of migrating cells. The aquaglyceroporin AQP3, which is found in normal epidermis and becomes upregulated in basal cell carcinoma, facilitates cell proliferation in different cell types. Remarkably, AQP3-null mice are resistant to skin tumorigenesis by a mechanism that may involve reduced tumor cell glycerol metabolism and ATP generation. Together, the data suggest that AQP expression in tumor cells and tumor vessels facilitates tumor growth and spread, suggesting AQP inhibition as a novel antitumor therapy.

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“…Aqp1 has been implicated recently in diverse cell migratory mechanisms such as wound healing and tumor spreading (Papadopoulos et al 2008), and aqp1 localized within the membrane of lamellipodia is suggested to facilitate local water influx resulting in membrane protrusion (Saadoun et al 2005). This mechanism works in concert with nmII-dependent force generation to focus tension at key adherence points, thus supporting cell migration (Papadopoulos et al 2008).…”

Section: Contractile Type III Fibrocytes Can Be Derived From the Cultmentioning

confidence: 99%

Contractility in Type III Cochlear Fibrocytes Is Dependent on Non-muscle Myosin II and Intercellular Gap Junctional Coupling

Kelly

Forge

Jagger

2012

JARO

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The cochlear spiral ligament is a connective tissue that plays diverse roles in normal hearing. Spiral ligament fibrocytes are classified into functional subtypes that are proposed to carry out specialized roles in fluid homeostasis, the mediation of inflammatory responses to trauma, and the fine tuning of cochlear mechanics. We derived a secondary sub-culture from guinea pig spiral ligament, in which the cells expressed protein markers of type III or "tension" fibrocytes, including non-muscle myosin II (nmII), α-smooth muscle actin (αsma), vimentin, connexin43 (cx43), and aquaporin-1. The cells formed extensive stress fibers containing αsma, which were also associated intimately with nmII expression, and the cells displayed the mechanically contractile phenotype predicted by earlier modeling studies. cx43 immunofluorescence was evident within intercellular plaques, and the cells were coupled via dye-permeable gap junctions. Coupling was blocked by meclofenamic acid (MFA), an inhibitor of cx43-containing channels. The contraction of collagen lattice gels mediated by the cells could be prevented reversibly by blebbistatin, an inhibitor of nmII function. MFA also reduced the gel contraction, suggesting that intercellular coupling modulates contractility. The results demonstrate that these cells can impart nmII-dependent contractile force on a collagenous substrate, and support the hypothesis that type III fibrocytes regulate tension in the spiral ligament-basilar membrane complex, thereby determining auditory sensitivity.

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

Cited by 668 publications

References 27 publications

Functions of aquaporins in the eye

Functions of aquaporins in the eye

Aquaporins—new players in cancer biology

Contractility in Type III Cochlear Fibrocytes Is Dependent on Non-muscle Myosin II and Intercellular Gap Junctional Coupling

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