Altered secretion of vascular signals changes extracellular matrix surrounding tumor cells
DOI: 10.1063/10.0009370
Altered secretion of vascular signals changes extracellular matrix surrounding tumor cells lead image
Altered expression of a signaling molecule called vascular endothelial growth factor (VEGF) has long been implicated as a common early event in the course of cancer metastasis. Such signaling disrupts the matrix-like glycocalyx that surrounds endothelial cells forming the blood vessel wall, but until now it has been unclear how VEGF affects tumor cell glycocalyx.
Xia et al. have elucidated the ultrastructural changes of the glycocalyx at endothelial and tumor cells that occur when VEGF is secreted. The investigators used super-resolution stochastic optical reconstruction microscopy to observe the spatio-chemical organizations of the heparan sulfate and hyaluronic acid within the glycocalyx of human cerebral microvascular endothelial cells and malignant breast cancer cells.
The work marks the first description of the differential effects of VEGF on the glycocalyx of endothelial and tumor cells.
“While VEGF disrupts endothelial glycocalyx to make blood vessel walls leaky, it enriches tumor cell glycocalyx to shield tumor cells from blood flow induced frictions and blood-borne therapeutic drugs,” said author Bingmei Fu. “Our finding elucidates the structural mechanism by which tumor secretion favors tumor metastasis in the microcirculation.”
While heparan sulfate lies perpendicular to the surface of regular endothelial cells, the group found it lies flat in the plane of tumor cells, weaving into a 2D network with hyaluronic acid covering the cell.
VEGF reduced the length and coverage of heparan sulfate at healthy endothelial cells but enhanced coverage of heparan sulfate and hyaluronic acid at the tumor cells, a difference that might help tumor cells metastasize.
The team aims to further investigate the role of the glycocalyx and VEGF in tumor cell adhesion and transmigration in microcirculation.
Source: “Differential effects of vascular endothelial growth factor on glycocalyx of endothelial and tumor cells and potential targets for tumor metastasis,” by Yifan Xia, Yunfei Li, and Bingmei Fu, APL Bioengineering (2022). The article can be accessed at https://doi.org/10.1063/5.0064381 .
