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

Abstract

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.

Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

“…To date, only a few cell mechanism studies have explored how HS, CS, HA, and SA regulate homing of cells, particularly white blood cells and cancer cells, from vessel circulation to the endothelium surface . Selected reports are summarized in Table , which shows that the majority of investigations have been performed in the context of white blood cells and inflammation, and more work is required in the cancer milieu to address metastasis . The white blood cell studies inform our understanding of GCX‐mediated EC adhesiveness to cancer cells, because cancer cells utilize inflammation mechanisms to metastasize and inflammatory agonists are known to cause endothelial GCX shedding that can expose endothelium to circulating cell adhesion.…”

Continuous dynamic modeling of regulated cell adhesion

“…The proposed approach uses adhesion forces that arise dynamically from CAM expression, instead from explicit cell types. Single-cell force spectroscopy can directly measure the adhesion forces between cells expressing different levels of CAMs (45), which can be used to experimentally set the parameters of the model. For simplicity, the model assume that the binding forces are proportional to the product of the relative concentration of CAMs; however, more complex formulations of adhesion ligands and receptors are also possible (46).…”

Fifteen years of Servitude et Grandeur to the application of a biophysical technique in medicine: The tale of AFMBioMed

“…A virtual issue appeared in the Journal of Molecular Recognition in 2017 . Nine research articles composed this special issue . At the end of the conference, it was announced that the next one will be organized in Kraków, in 2017.…”

“…[48][49][50][51][52][53][54][55][56][57] The last change that was made during the 75 Nine research articles composed this special issue. [76][77][78][79][80][81][82][83][84] At the end of the conference, it was announced that the next one will…”