Comparative Therapeutic Validation of a Microfluidic Metastasis Model: Cimetidine but Not Cilengitide Inhibits Physiological Tumor Cell Extravasation.
- 1Department of Biochemical Engineering, UCL University College London, London WC1E 6BT, UK.
- 2Department of Health, Medical and Life Sciences, HFU Hochschule Furtwangen, 78054 Villingen-Schwenningen, Germany.
Abstract
Interactions between tumor cells and the endothelial lining of blood vessels under flow conditions are essential for successful metastasis. These interactions are mainly facilitated by adhesive proteins, like integrins or selectins and by proteases. While expression of specific integrins (αvβ₃ and αvβ₅) and selectins correlate with tumor progression in cancer and seem to mediate tumor cell adhesion, analysis of a therapeutic intervention in these processes is frequently limited to systems lacking physiological cell-cell interactions. In this study on the adhesion of different tumor cell types in monoculture and in coculture on endothelial cell layers was evaluated under different conditions, i.e., different static setups and under flow conditions in a microfluidic device and under treatment with the integrin inhibitor Cilengitide and the selectin inhibitor Cimetidine. This careful comparative experimental validation revealed that while Cilengitide inhibits H838-, HCT116- and U87-tumor cell adhesion in tumor cell monocultures in all assay set-ups its effect is abolished by the presence of endothelial cells. In contrast, Cimetidine, a Histamine 2 receptor antagonist and E-selectin inhibitor significantly reduced H838 lung carcinoma cell adhesion and trans-endothelial migration suggesting a significant role of E-selectin in tumor progressions and metastasis.
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BibTeX
@article{kuhlbach2026comparative,
title = {{Comparative Therapeutic Validation of a Microfluidic Metastasis Model: Cimetidine but Not Cilengitide Inhibits Physiological Tumor Cell Extravasation.}},
author = {Claudia Kühlbach and Lea Olschewski and Frank Baganz and Volker C Hass and Margareta M Mueller},
journal = {Bioengineering (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/bioengineering13101192},
url = {https://europepmc.org/article/MED/42939047},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative Therapeutic Validation of a Microfluidic Metastasis Model: Cimetidine but Not Cilengitide Inhibits Physiological Tumor Cell Extravasation.
AU - Claudia Kühlbach
AU - Lea Olschewski
AU - Frank Baganz
AU - Volker C Hass
AU - Margareta M Mueller
PY - 2026
DA - 2026/10/14
JO - Bioengineering (Basel, Switzerland)
DO - 10.3390/bioengineering13101192
UR - https://europepmc.org/article/MED/42939047
AB - Interactions between tumor cells and the endothelial lining of blood vessels under flow conditions are essential for successful metastasis. These interactions are mainly facilitated by adhesive proteins, like integrins or selectins and by proteases. While expression of specific integrins (αvβ₃ and αvβ₅) and selectins correlate with tumor progression in cancer and seem to mediate tumor cell adhesion, analysis of a therapeutic intervention in these processes is frequently limited to systems lacking physiological cell-cell interactions. In this study on the adhesion of different tumor cell types in monoculture and in coculture on endothelial cell layers was evaluated under different conditions, i.e., different static setups and under flow conditions in a microfluidic device and under treatment with the integrin inhibitor Cilengitide and the selectin inhibitor Cimetidine. This careful comparative experimental validation revealed that while Cilengitide inhibits H838-, HCT116- and U87-tumor cell adhesion in tumor cell monocultures in all assay set-ups its effect is abolished by the presence of endothelial cells. In contrast, Cimetidine, a Histamine 2 receptor antagonist and E-selectin inhibitor significantly reduced H838 lung carcinoma cell adhesion and trans-endothelial migration suggesting a significant role of E-selectin in tumor progressions and metastasis.
SN - 2306-5354
ER -