The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells

Krähling, Hermann; Mally, Sabine; Eble, Johannes A.; Noël, Jean-François; Schwab, Albrecht; Stock, Christian

doi:10.1007/s00424-009-0694-7

Cited by 50 publications

(52 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These pH-environments are stabilized by the glycocalix (23). Particularly at focal adhesions at the cell front, the pericellular H + concentration is high.…”

Section: The Ecm Composition Arranges Motility and Invasionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Vahle

Domikowsky

Schwöppe

et al. 2013

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Abstract. The activity of the Na + /H + exchanger NHE1 is required for human melanoma cell adhesion and migration. The goal of the present study was to suppress mouse melanoma (B16V) cell invasion in vivo by inhibiting NHE1. Intravital observations in mobilized left liver lobes of laparotomized male Sprague-Dawley rats disclosed that five minutes after intra-arterial administration of the B16V cell suspension, cells adhered to the endothelia of liver sinusoidal capillaries and started to migrate into the surrounding liver tissue. In the presence of the NHE1-specific inhibitor cariporide, migration/invasion was reduced by about 50% while adhesion was not lowered. Time-lapse video microscopy and adhesion/invasion assays revealed that in vitro, blockade of NHE1 by cariporide i) significantly decreased the migratory speed of the cells and ii) completely inhibited the invasive behavior of both an artificial, basement membrane-like and a dermis-like matrix. Cells were more motile on the basement membrane and more invasive on the dermis-like matrix. Small-animal PET (positron-emission tomography) analyses of B16V metastasis in female C57BL/6 mice showed that, although NHE1 inhibition hardly affected the percentage of animals developing metastases or relapses, metastases seem to get directed to the lungs in cariporide-treated animals while animals feeding on the standard diet show metastases spread all over the body. We conclude that i) B16V cells prefer to invade a dermis-like rather than a basement membranelike matrix; ii) the extracellular matrix (ECM) composition strongly impacts on NHE1-dependent in vitro cell motility and invasion; and iii) the lungs are metastasis-prone and impair the efficiency of cariporide due to their ECM composition and the pulmonary interstitial (extravascular) pH.

show abstract

“…These pH-environments are stabilized by the glycocalix (23). Particularly at focal adhesions at the cell front, the pericellular H + concentration is high.…”

Section: The Ecm Composition Arranges Motility and Invasionmentioning

confidence: 99%

“…Both, adhesion to the ECM as well as its digestion require an optimum pH at the cell surface (22). In addition to the overall proton concentration present in the stroma, NHE1 activity represents a tunable proton source (15,23,24).…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Vahle

Domikowsky

Schwöppe

et al. 2013

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Multiple integrins, such as a 2 b 1 , a 5 b 1 or a n b 3 , are pH-dependent in melanoma [19] and in other cells [66,67]. Increased adhesion at acidic extracellular pH values is explained by conformational changes that lead to an enhanced aviditity of the integrin headpieces to ECM proteins [67] or by a pH dependence of the mechanical stability of focal adhesions [68].…”

Section: Ionic Mechanisms Of Cell Migrationmentioning

confidence: 99%

“…Conceptually, it is important that integrins protrude only 20 nm into the extracellular space [69]. Therefore, it is not surprising that the pericellular pH e inside the glycocalyx is more important for cell adhesion than the pH of the extracellular bulk solution surrounding migrating melanoma cells [19,21]. The pericellular pH e even confers asymmetry upon migrating tumour cells, because it is more acidic at the cell front than at the rear end [21,28].…”

Section: Ionic Mechanisms Of Cell Migrationmentioning

confidence: 99%

Ion channels and transporters in tumour cell migration and invasion

Schwab

Stock

2014

Phil. Trans. R. Soc. B

Self Cite

117

View full text Add to dashboard Cite

Cell migration is a central component of the metastatic cascade requiring a concerted action of ion channels and transporters (migration-associated transportome), cytoskeletal elements and signalling cascades. Ion transport proteins and aquaporins contribute to tumour cell migration and invasion among other things by inducing local volume changes and/or by modulating Ca 2þ and H þ signalling. Targeting cell migration therapeutically bears great clinical potential, because it is a prerequisite for metastasis. Ion transport proteins appear to be attractive candidate target proteins for this purpose because they are easily accessible as membrane proteins and often overexpressed or activated in cancer. Importantly, a number of clinically widely used drugs are available whose anticipated efficacy as anti-tumour drugs, however, has now only begun to be evaluated.

show abstract

“…His group found that the Na + /H + exchanger NHE1 is necessary for the migration of cultured human melanoma cells and acts through 1 integrin at the front of the cell to promote attachment to the substrate. This attachment is necessary for cell movement (Krahling et al, 2009). NHE1 is part of the focal adhesion contacts and accumulates at the cell front where its activity causes acidification at the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Modeling new conceptual interpretations of development

Vermot

Affolter

2011

Development

View full text Add to dashboard Cite

approaches combined with modeling were the predominantly discussed tools. In addition, the meeting featured efforts to combine several disciplines in order to address questions concerning growth, morphogenesis and patterning from a dynamic point of view. Talks were highly diverse, from ion dynamics and regeneration to cellular mechanodetection and transduction. In addition, numerous new conceptual advances in coupling physical forces and morphogenesis, as well as the development of novel technologies to study forces, were discussed. The researchers attending the meeting agreed that the combined use of modeling and imaging approaches is key to ensuring the quality of measurements and the validity of the models developed using these measurements. Another emerging theme was the importance of the physical input and mechanical forces in developmental processes, as well as their interactions with the genetic program at work in the embryo. The embryo gets biophysicalIn growing tissues, cells experience a mix of tensile forces and chemical information. Key to untangling the possible links, as well as the causality, between the two is the ability to measure and map the physical properties of tissues at the cellular level and characterize their biological effects. Overall, these measures need to be made using innovative technologies, the challenge being the ability to explore dynamics of developmental events.Clues as to how to address some of these issues were provided by Jochen Guck (University of Cambridge, UK), who studies the viscoelastic properties of tissues and their influences on cell behavior during central nervous system (CNS) development. His group has developed an approach using quantitative scanning force microscopy (through atomic force microscopy, AFM) to measure CNS tissue compliance. Owing to the heterogeneities of this tissue, glial cells and neurons can behave rather differently during their migration, as this process is mechano-dependant . To address the mechanical properties of tissues and cell behavior in response to their physical constraints, Guck's group created compliant polyacrylamide gel surfaces that are of varying stiffness that match or exceeds the stiffness of CNS tissues. They showed that, depending on their identity, cells will react differently to the stiffness of the environment: astrocytes and microglia will change shape if they are in contact with stiff substrates, whereas neurons will do so to a much lesser extent. Nevertheless, the migration of neurons is highly dependent on stiffness, as neurons tend to migrate towards soft tissue. By contrast, microglia move toward stiffer substrates. Importantly, astrocytes and microglia in stiff environments react by upregulating inflammatory mediators ). Guck's results show that the growth cone is also sensitive to its environment, as it retracts when in contact with the mechanical stimulation of the AFM probe. Guck suggested that the mechanical mismatch between neural implants and native tissue might be at the root of foreign body reaction and...

show abstract

The glycocalyx maintains a cell surface pH nanoenvironment crucial for integrin-mediated migration of human melanoma cells

Cited by 50 publications

References 43 publications

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Extracellular matrix composition and interstitial pH modulate NHE1-mediated melanoma cell motility

Ion channels and transporters in tumour cell migration and invasion

Modeling new conceptual interpretations of development

Contact Info

Product

Resources

About