Loss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endothelium

Rai, Srijana; Nejadhamzeeigilani, Zaynab; Gutowski, Nicholas J.; Whatmore, Jacqueline L.

doi:10.1186/s13046-015-0223-9

Cited by 46 publications

(65 citation statements)

References 38 publications

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“…Remarkably, the EC adhesion 15 molecules identified (e.g. selectins, ICAM-1, VCAM-1 [16][17][18] ) are strongly associated with EC activation, 16 bringing into question the requirement of pre-existing inflammation for extravasation. Regardless, 17 cell adhesion is not only controlled through surface expression of specific receptors, but also by the 18 glycocalyx (GCX), a ubiquitous surface coating of glycoproteins and proteoglycans.…”

Section: Introductionmentioning

confidence: 99%

Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells

Offeddu

Hajal

Foley

et al. 2020

Preprint

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The glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a novel mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Transendothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

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Section: Introductionmentioning

confidence: 99%

Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells

Offeddu

Hajal

Foley

et al. 2020

Preprint

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“…The precise reasons behind the stiffening and adhesion stabilization phenomena in glycocalyx degraded cells remain to be elucidated. We presently consider that the time left to observe apoptotic effects induced by glycocalyx degradation is too short (about 30 min, see Materials and methods) (Rai et al 2015). Interestingly, the PL model reflects the mechanical effect depicted above, but not the totality of adhesion effect observed in glycocalyx degraded cells after PFC exposure.…”

Section: Effect Of Glycocalyx Degradation On Cell Responsementioning

confidence: 96%

“…Coverslides are mounted on a slide with the cell side down in prolong (Thermo Fisher). Glycocalyx distribution is evaluated in live cells by staining glycocalyx using fluorescein isothiocyanate-labeled wheat germ agglutinin (WGA-FITC) at 5 µg/ml incubated for 10 min at 37 • C, 5% CO 2 −95% air atmosphere as in Rai et al (2015). Images are acquired on fluorescent transmission microscope AxioVert 200 (Zeiss) at 50× magnification.…”

Section: Staining Of F-actin Focal Adhesion and Glycocalyxmentioning

confidence: 99%

Perfluorocarbon induces alveolar epithelial cell response through structural and mechanical remodeling

Dias¹,

Planus²,

Angely³

et al. 2018

Biomech Model Mechanobiol

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During total liquid ventilation, lung cells are exposed to perfluorocarbon (PFC) whose chemophysical properties highly differ from standard aqueous cell feeding medium (DMEM). We herein perform a systematic study of structural and mechanical properties of A549 alveolar epithelial cells in order to characterize their response to PFC exposure, using DMEM as control condition. Changes in F-actin structure, focal adhesion density and glycocalyx distribution are evaluated by confocal fluorescent microscopy. Changes in cell mechanics and adhesion are measured by multiscale magnetic twisting cytometry (MTC). Two different microrheological models (single Voigt and power law) are used to analyze the cell mechanics characterized by cytoskeleton (CSK) stiffness and characteristic relaxation times. Cell-matrix adhesion is analyzed using a stochastic multibond deadhesion model taking into account the non-reversible character of the cell response, allowing us to quantify the adhesion weakness and the number of associated bonds. The roles of F-actin structure and glycocalyx layer are evaluated by depolymerizing F-actin and degrading glycocalyx, respectively. Results show that PFC exposure consistently induces F-actin remodeling, CSK softening and adhesion weakening. These results demonstrate that PFC triggers an alveolar epithelial cell response herein evidenced by a decay in intracellular CSK tension, an adhesion weakening and a glycocalyx layer redistribution. These PFC-induced cell adjustments are consistent with the hypothesis that cells respond to a decrease in adhesion energy at cell surface. This adhesion energy can be even further reduced in the presence of surfactant adsorbed at the cell surface.

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“…The local changes of ion concentration, pH or inflammation can influence the structure of endothelial glycocalyx, as a consequence significantly enhance the metastatic potential . Rai et al reports that the loss of the endothelial glycocalyx is associated with an increased selectin mediated adhesion of A549 …”

Section: Introductionmentioning

confidence: 99%

“…22,23 Rai et al reports that the loss of the endothelial glycocalyx is associated with an increased selectin mediated adhesion of A549. 24 Single-cell AFM spectroscopy is a method that enables direct monitoring of the cell-to-cell interaction. 25 Single-cell AFM spectroscopy has been used to study diverse biological process, such as immunological ligand-receptor interactions 26,27 or lymphocyte-endothelial interactions under inflammatory conditions.…”

mentioning

confidence: 99%

The impact of hyperglycemia on adhesion between endothelial and cancer cells revealed by single‐cell force spectroscopy

Malek-Zietek

Targosz‐Korecka

Szymoński

2017

J of Molecular Recognition

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The impact of hyperglycemia on adhesion between lung carcinoma cells (A549) and pulmonary human aorta endothelial cells (PHAEC) was studied using the single-cell force spectroscopy. Cancer cells were immobilized on a tipless Atomic Force Microscopy (AFM) cantilever and a single layer of endothelial cells was prepared on a glass slide. The measured force-distance curves provided information about the detachment force and about the frequency of specific ligand-receptor rupture events. Measurements were performed for different times of short term (up to 2 h) and prolonged hyperglycemia (3 h - 24 h). Single-cell force results were correlated with the expression of cell adhesion molecules (intercellular adhesion molecule, P-selectin) and with the length and density of the PHAECs glycocalyx layer, which were measured by AFM nanoindentation. For short-term hyperglycemia, we observed a statistically significant increase of the adhesion parameters that was accompanied by an increase of the glycocalyx length and expression of P-selectin. Removal of hyaluronic acid from PHAECs glycocalyx significantly decreased the adhesion parameters, which indicates that hyaluronic acid has a strong impact on adhesion in A549/PHAEC system in short term of hyperglycemia. For prolonged hyperglycemia, the most significant increase of adhesion parameters was observed for 24 hours and this phenomenon correlated with the expression of adhesion molecules and a decrease of the glycocalyx length. Taking together, presented data indicate that both mechanical and structural properties of the endothelial glycocalyx strongly modulate the adhesion in the A549/PHAEC system.

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Loss of the endothelial glycocalyx is associated with increased E-selectin mediated adhesion of lung tumour cells to the brain microvascular endothelium

Cited by 46 publications

References 38 publications

Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells

Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells

Perfluorocarbon induces alveolar epithelial cell response through structural and mechanical remodeling

The impact of hyperglycemia on adhesion between endothelial and cancer cells revealed by single‐cell force spectroscopy

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