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Metformin attenuates adhesion between cancer and endothelial cells in chronic hyperglycemia by recovery of the endothelial glycocalyx barrier.
- Source :
-
Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2020 Apr; Vol. 1864 (4), pp. 129533. Date of Electronic Publication: 2020 Jan 15. - Publication Year :
- 2020
-
Abstract
- Background: Epidemiologic studies suggest that diabetes is associated with an increased risk of cancer. Concurrently, clinical trials have shown that metformin, which is a first-line antidiabetic drug, displays anticancer activity. The underlying mechanisms for these effects are, however, still not well recognized.<br />Methods: Methods based on atomic force microscopy (AFM) were used to directly evaluate the influence of metformin on the nanomechanical and adhesive properties of endothelial and cancer cells in chronic hyperglycemia. AFM single-cell force spectroscopy (SCFS) was used to measure the total adhesion force and the work of detachment between EA.hy926 endothelial cells and A549 lung carcinoma cells. Nanoindentation with a spherical AFM probe provided information about the nanomechanical properties of cells, particularly the length and grafting density of the glycocalyx layer. Fluorescence imaging was used for glycocalyx visualization and monitoring of E-selectin and ICAM-1 expression.<br />Results: SCFS demonstrated that metformin attenuates adhesive interactions between EA.hy926 endothelial cells and A549 lung carcinoma cells in chronic hyperglycemia. Nanoindentation experiments, confirmed by confocal microscopy imaging, revealed metformin-induced recovery of endothelial glycocalyx length and density. The recovery of endothelial glycocalyx was correlated with a decrease in the surface expression of E-selectin and ICAM-1.<br />Conclusion: Our results identify metformin-induced endothelial glycocalyx restoration as a key factor responsible for the attenuation of adhesion between EA.hy926 endothelial cells and A549 lung carcinoma cells.<br />General Significance: Metformin-induced glycocalyx restoration and the resulting attenuation of adhesive interactions between the endothelium and cancer cells may account for the antimetastatic properties of this drug.<br /> (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- A549 Cells
Adenocarcinoma, Bronchiolo-Alveolar pathology
Cell Adhesion drug effects
Cells, Cultured
Chronic Disease
Endothelial Cells pathology
Endothelium drug effects
Endothelium metabolism
Glycocalyx drug effects
Glycocalyx metabolism
Humans
Hyperglycemia pathology
Lung Neoplasms pathology
Microscopy, Atomic Force
Adenocarcinoma, Bronchiolo-Alveolar drug therapy
Antineoplastic Agents pharmacology
Endothelial Cells drug effects
Hyperglycemia drug therapy
Hypoglycemic Agents pharmacology
Lung Neoplasms drug therapy
Metformin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8006
- Volume :
- 1864
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. General subjects
- Publication Type :
- Academic Journal
- Accession number :
- 31953127
- Full Text :
- https://doi.org/10.1016/j.bbagen.2020.129533