Vascular laminins in physiology and pathology

Russo, Jacopo Di; Hannocks, Melanie-Jane; Luik, Anna-Liisa; Song, Jian; Zhang, Xueli; Yousif, Lema F.; Aspite, Gunita; Hallmann, Rupert; Sorokin, Lydia

doi:10.1016/j.matbio.2016.06.008

Cited by 52 publications

(53 citation statements)

References 69 publications

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“…We confirmed by immunocytochemistry and confocal microscopy, our previous electron microscope studies that, within 5 min of injection into the CSF, tracer were present in the brain within basement membranes on the outer aspects of cortical artery walls. More exactly, the electron microscope study [24] and the present results using immunocytochemistry for α-2 laminin [9] identified tracer in pial-glial basement membranes. These results suggest that one pathway for entry of tracers into the brain from the CSF is along the pial-glial basement membranes between the layer of pia mater and astrocytes in the perivascular glia limitans (Fig.…”

Section: Discussionsupporting

confidence: 58%

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Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

et al. 2018

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Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the “glymphatic system” that proposes tracers enter the brain along periarterial “spaces” and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular “spaces” around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. 2 μL of 100 μM soluble, fluorescent fixable amyloid β (Aβ) were injected into the CSF of the cisterna magna of 6–10 and 24–30 month-old male mice and their brains were examined 5 and 30 min later. At 5 min, immunocytochemistry and confocal microscopy revealed Aβ on the outer aspects of cortical arteries colocalized with α-2 laminin in the pial-glial basement membranes. At 30 min, Aβ was colocalised with collagen IV in smooth muscle cell basement membranes in the walls of cortical arteries corresponding to the IPAD pathways. No evidence for drainage along the walls of veins was found. Measurements of the depth of penetration of tracer were taken from 11 regions of the brain. Maximum depths of penetration of tracer into the brain were achieved in the pons and caudoputamen. Conclusions drawn from the present study are that tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. The exit route is along IPAD pathways in which Aβ accumulates in cerebral amyloid angiopathy (CAA) in Alzheimer’s disease. Results from this study suggest that CSF may be a suitable route for delivery of therapies for neurological diseases, including CAA.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1862-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 58%

“…BM4 pia-glial basement membrane between the pia mater and the astrocytes of the glia limitans. In this study, BM4 is identified by the presence of α2-laminin [9, 13]. Proposed route of IPAD tracer is located in the capillary endothelial basement membrane (5) apparently entering from the brain parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

et al. 2018

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“…Besides laminin 111, type-IV collagen, nidogen, perlecan and fibronectin, which were present in both astrocyte-deposited ECM and rBM, laminin α5 was detected in astrocyte cultures but largely absent in rBM (Hughes et al, 2010). Laminin α5 contributes to laminin 511, the predominant isoform in basement membranes of brain blood vessels (Di Russo et al, 2017;Wu et al, 2009). To test whether laminin 511 accounts for integrin-dependent or integrinindependent glioma-cell-matrix interactions, cell culture plastic coated with human recombinant laminin 511 was used as a migration substrate.…”

Section: Resultsmentioning

confidence: 99%

“…Glioma cell invasion occurs along defined tissue structures, including white matter tracks comprising myelinated axons and astrocyte processes, forming topologically complex cellular networks filled with hydrated, soft extracellular matrix (ECM) composed of hyaluronan and proteoglycans (Cuddapah et al, 2014;Gritsenko et al, 2012;Miyata and Kitagawa, 2017). As an alternative invasion route, brain blood vessels provide a particularly permissive niche of confined space between vascular basement membranes and adjacent brain stroma, which are molecularly and physically complex types of confined space (Di Russo et al, 2017;Farin et al, 2006;Gritsenko et al, 2012;Watkins et al, 2014). To interact with structural basement membrane proteins, glioma cells depend upon integrin adhesion receptors, including: α3β1, α6β1, α6β4 and α7β1 binding to laminins, α1β1 and α2β1 interacting with type-IV collagen (Kawataki et al, 2007;Khoshnoodi et al, 2008;Ramovs et al, 2017;Yurchenco, 2011Yurchenco, , 2015, and αVβ3 engaging with both laminin and type IV collagen (Pedchenko et al, 2004;Sasaki and Timpl, 2001;Xu et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Adaptive adhesion systems mediate glioma cell invasion in complex environments

Gritsenko

Friedl

2018

Journal of Cell Science

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Diffuse brain invasion by glioma cells prevents effective surgical or molecular-targeted therapy and underlies a detrimental outcome. Migrating glioma cells are guided by complex anatomical brain structures but the exact mechanisms remain poorly defined. To identify adhesion receptor systems and matrix structures supporting glioma cell invasion into brain-like environments we used 2D and 3D organotypic invasion assays in combination with antibody-, peptide- and RNA-based interference. Combined interference with β1 and αV integrins abolished the migration of U-251 and E-98 glioma cells on reconstituted basement membrane; however, invasion into primary brain slices or 3D astrocyte-based scaffolds and migration on astrocyte-deposited matrix was only partly inhibited. Any residual invasion was supported by vascular structures, as well as laminin 511, a central constituent of basement membrane of brain blood vessels. Multi-targeted interference against β1, αV and α6 integrins expressed by U-251 and E-98 cells proved insufficient to achieve complete migration arrest. These data suggest that mechanocoupling by integrins is relatively resistant to antibody- or peptide-based targeting, and cooperates with additional, as yet unidentified adhesion systems in mediating glioma cell invasion in complex brain stroma.

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“…Other studies report a complementary function for laminin α4 and α5: laminin α4 knockout mice show bleeding during embryogenesis resulting in a perinatal anemia, which is rescued 3 to 4 weeks postnatally once laminin α5 expression is turned on [105]. It has also been suggested that laminin 511 is required to maintain the β 1 integrin-dependent anchorage of ECs in shear stress conditions and thus may be important to the formation of functional vessels [106,107]. In 3D EC cultures laminin is required for EC aggregation in end-to-end networks and the effect is α 6 integrin dependent; the engagement of α 6 integrin by laminin increases Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) expression and Vascular Endothelial Growth Factor (VEGF) uptake by EC [108].…”

Section: Laminins: Multiple Chains For Multiple Functionsmentioning

confidence: 99%

Extracellular Matrix, a Hard Player in Angiogenesis

Mongiat

Andreuzzi

Tarticchio

et al. 2016

IJMS

172

133

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The extracellular matrix (ECM) is a complex network of proteins, glycoproteins, proteoglycans, and polysaccharides. Through multiple interactions with each other and the cell surface receptors, not only the ECM determines the physical and mechanical properties of the tissues, but also profoundly influences cell behavior and many physiological and pathological processes. One of the functions that have been extensively explored is its impingement on angiogenesis. The strong impact of the ECM in this context is both direct and indirect by virtue of its ability to interact and/or store several growth factors and cytokines. The aim of this review is to provide some examples of the complex molecular mechanisms that are elicited by these molecules in promoting or weakening the angiogenic processes. The scenario is intricate, since matrix remodeling often generates fragments displaying opposite effects compared to those exerted by the whole molecules. Thus, the balance will tilt towards angiogenesis or angiostasis depending on the relative expression of pro- or anti-angiogenetic molecules/fragments composing the matrix of a given tissue. One of the vital aspects of this field of research is that, for its endogenous nature, the ECM can be viewed as a reservoir to draw from for the development of new more efficacious therapies to treat angiogenesis-dependent pathologies.

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Vascular laminins in physiology and pathology

Cited by 52 publications

References 69 publications

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

Adaptive adhesion systems mediate glioma cell invasion in complex environments

Extracellular Matrix, a Hard Player in Angiogenesis

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