Non-collagenous ECM proteins in blood vessel morphogenesis and cancer

Kostourou, Vassiliki; Papalazarou, Vasileios

doi:10.1016/j.bbagen.2014.02.018

Cited by 32 publications

(26 citation statements)

References 121 publications

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“…[10][11][12] Adhesion of endothelial cells to the vascular ECM occurs through various transmembrane adhesion receptors, in particular via integrins. 13,14 Integrins sense the composition and rigidity of the ECM. Their interaction with ECM components triggers the…”

Section: See Cover Imagementioning

confidence: 99%

F-Actin–Anchored Focal Adhesions Distinguish Endothelial Phenotypes of Human Arteries and Veins

Geemen

Smeets

Stalborch

et al. 2014

ATVB

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Objective-Vascular endothelial-cadherin-and integrin-based cell adhesions are crucial for endothelial barrier function.Formation and disassembly of these adhesions controls endothelial remodeling during vascular repair, angiogenesis, and inflammation. In vitro studies indicate that vascular cytokines control adhesion through regulation of the actin cytoskeleton, but it remains unknown whether such regulation occurs in human vessels. We aimed to investigate regulation of the actin cytoskeleton and cell adhesions within the endothelium of human arteries and veins. Approach and Results-We used an ex vivo protocol for immunofluorescence in human vessels, allowing detailed en face microscopy of endothelial monolayers. We compared arteries and veins of the umbilical cord and mesenteric, epigastric, and breast tissues and find that the presence of central F-actin fibers distinguishes the endothelial phenotype of adult arteries from veins. F-actin in endothelium of adult veins as well as in umbilical vasculature predominantly localizes cortically at the cell boundaries. By contrast, prominent endothelial F-actin fibers in adult arteries anchor mostly to focal adhesions containing integrin-binding proteins paxillin and focal adhesion kinase and follow the orientation of the extracellular matrix protein fibronectin. Other arterial F-actin fibers end in vascular endothelial-cadherin-based endothelial focal adherens junctions. In vitro adhesion experiments on compliant substrates demonstrate that formation of focal adhesions is strongly induced by extracellular matrix rigidity, irrespective of arterial or venous origin of endothelial cells. Conclusions-Our data show that F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries from veins. We conclude that the biomechanical properties of the vascular extracellular matrix determine this endothelial characteristic. (Arterioscler Thromb Vasc

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Section: See Cover Imagementioning

confidence: 99%

F-Actin–Anchored Focal Adhesions Distinguish Endothelial Phenotypes of Human Arteries and Veins

Geemen

Smeets

Stalborch

et al. 2014

ATVB

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“…It has long been known that cells can migrate up a gradient of adhered substrate (haptotaxis) in vitro (Carter, 1965), but the cellular and molecular mechanisms of this process are poorly understood. Haptotaxis is likely to contribute to many physiological and pathophysiological events, such as cutaneous wound healing (Sawicka et al, 2015;Clark, 1990), response to cardiovascular disease (Takawale et al, 2015), atherosclerosis and cancer progression (Kostourou and Papalazarou, 2014;Aznavoorian et al, 1990;Wolf and Friedl, 2011). Understanding the mechanism of haptotaxis will be crucial for dissecting the relative contributions of various directional migration cues during these events.…”

Section: Introductionmentioning

confidence: 99%

Lamellipodia are crucial for haptotactic sensing and response

King

Asokan

Haynes

et al. 2016

Journal of Cell Science

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Haptotaxis is the process by which cells respond to gradients of substrate-bound cues, such as extracellular matrix proteins (ECM); however, the cellular mechanism of this response remains poorly understood and has mainly been studied by comparing cell behavior on uniform ECMs with different concentrations of components. To study haptotaxis in response to gradients, we utilized microfluidic chambers to generate gradients of the ECM protein fibronectin, and imaged the cell migration response. Lamellipodia are fan-shaped protrusions that are common in migrating cells. Here, we define a new function for lamellipodia and the cellular mechanism required for haptotaxisdifferential actin and lamellipodial protrusion dynamics lead to biased cell migration. Modest differences in lamellipodial dynamics occurring over time periods of seconds to minutes are summed over hours to produce differential whole cell movement towards higher concentrations of fibronectin. We identify a specific subset of lamellipodia regulators as being crucial for haptotaxis. Numerous studies have linked components of this pathway to cancer metastasis and, consistent with this, we find that expression of the oncogenic Rac1 P29S mutation abrogates haptotaxis. Finally, we show that haptotaxis also operates through this pathway in 3D environments.

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“…Laminin molecules are heterotrimeric glycoproteins consisting of one α, one β, and one γ chain held together by disulfide bonds [9] (Fig. 7.1b).…”

Section: Structural Ecm Proteinsmentioning

confidence: 99%