Fibrin microstructures reveal differential pericellular fibrin degradation in breast cancer cells.
- 1W. H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, 950 Atlantic Dr NW Ste 1, Atlanta, Georgia, 30332, United States.
- 2Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, Georgia, 30332, United States.
Abstract
Deciphering the regulation of localized proteolytic activity of cancer cells requires convenient and robust readouts of proteolytic activity. Toward this end, this paper describes a printed fibrin microstructure degradation analysis workflow with time lapse imaging based, parallelized measurement of pericellular fibrin degradation. This workflow is applied to two types of breast cancer cells and a normal mammary epithelial cell line. The baseline pericellular fibrin degradation activity as well as response upon exposure to bacteria-derived lipopolysaccharide (LPS), varies significantly between these cell types. Recombinant plasminogen activator inhibitor 1 (PAI1), which inhibits production of the main fibrinolytic protease plasmin, dose dependently inhibits fibrin degradation by the two breast cancer cell lines but has only a small effect on the normal epithelial cell line consistent with reports that normal cells generally have lower plasminogen activator expression than cancer cells. Interestingly, all the epithelial cell lines degrade the fibrin microstructures in a minimal media that excludes the plasminogen containing serum, suggesting sensitivity of this assay to the activity of fibrin-degrading enzymes other than plasmin. This workflow of determining plasmin and non-plasmin mediated as well as cell context dependent pericellular fibrin degrading activity, when applied to a previously reported endothelial fibrin degradation assay reconfirms the highly plasmin dependent nature of endothelial cell fibrin degradation while newly revealing significant fibrin degradation enhancing effects of VEGF and FGF. This expanded and updated fibrin microstructure degradation assay workflow clearly visualizes previously underappreciated cell type and cell context dependence of pericellular fibrin degrading activity with implications for breast cancer studies and beyond.
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BibTeX
@article{hamilton2026fibrin,
title = {{Fibrin microstructures reveal differential pericellular fibrin degradation in breast cancer cells.}},
author = {Jamie A G Hamilton and Nathan Ocampo and Soojung Lee and Shuichi Takayama},
journal = {Biomaterials and biosystems},
year = {2026},
month = oct,
doi = {10.1016/j.bbiosy.2026.100152},
url = {https://europepmc.org/article/MED/42999629},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Fibrin microstructures reveal differential pericellular fibrin degradation in breast cancer cells.
AU - Jamie A G Hamilton
AU - Nathan Ocampo
AU - Soojung Lee
AU - Shuichi Takayama
PY - 2026
DA - 2026/10/19
JO - Biomaterials and biosystems
DO - 10.1016/j.bbiosy.2026.100152
UR - https://europepmc.org/article/MED/42999629
AB - Deciphering the regulation of localized proteolytic activity of cancer cells requires convenient and robust readouts of proteolytic activity. Toward this end, this paper describes a printed fibrin microstructure degradation analysis workflow with time lapse imaging based, parallelized measurement of pericellular fibrin degradation. This workflow is applied to two types of breast cancer cells and a normal mammary epithelial cell line. The baseline pericellular fibrin degradation activity as well as response upon exposure to bacteria-derived lipopolysaccharide (LPS), varies significantly between these cell types. Recombinant plasminogen activator inhibitor 1 (PAI1), which inhibits production of the main fibrinolytic protease plasmin, dose dependently inhibits fibrin degradation by the two breast cancer cell lines but has only a small effect on the normal epithelial cell line consistent with reports that normal cells generally have lower plasminogen activator expression than cancer cells. Interestingly, all the epithelial cell lines degrade the fibrin microstructures in a minimal media that excludes the plasminogen containing serum, suggesting sensitivity of this assay to the activity of fibrin-degrading enzymes other than plasmin. This workflow of determining plasmin and non-plasmin mediated as well as cell context dependent pericellular fibrin degrading activity, when applied to a previously reported endothelial fibrin degradation assay reconfirms the highly plasmin dependent nature of endothelial cell fibrin degradation while newly revealing significant fibrin degradation enhancing effects of VEGF and FGF. This expanded and updated fibrin microstructure degradation assay workflow clearly visualizes previously underappreciated cell type and cell context dependence of pericellular fibrin degrading activity with implications for breast cancer studies and beyond.
SN - 2666-5344
ER -