Real-Time Measurement of Melanoma Cell-Mediated Human Brain Endothelial Barrier Disruption Using Electric Cell-Substrate Impedance Sensing Technology
Autor: | Akshata Anchan, Dan T Kho, Rebecca Johnson, Panagiota Kalogirou-Baldwin, Catherine E. Angel, James J W Hucklesby, Wayne R. Joseph, Simon J. O'Carroll, Graeme J. Finlay, E Scott Graham |
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Rok vydání: | 2019 |
Předmět: |
Skin Neoplasms
Time Factors Endothelium endothelium lcsh:Biotechnology Clinical Biochemistry Biosensing Techniques Blood–brain barrier blood–brain barrier 01 natural sciences Article Electric cell-substrate impedance sensing 03 medical and health sciences 0302 clinical medicine lcsh:TP248.13-248.65 medicine Electric Impedance Humans Melanoma Barrier function ECIS Chemistry 010401 analytical chemistry Brain Endothelial Cells General Medicine Human brain medicine.disease 0104 chemical sciences Cell biology medicine.anatomical_structure Blood-Brain Barrier 030220 oncology & carcinogenesis Paracellular transport Cancer cell impedance barrier function |
Zdroj: | Biosensors Biosensors, Vol 9, Iss 2, p 56 (2019) Volume 9 Issue 2 |
ISSN: | 2079-6374 |
Popis: | Electric cell-substrate impedance sensing (ECIS) is an impedance-based method for monitoring changes in cell behaviour in real-time. In this paper, we highlight the importance of ECIS in measuring the kinetics of human melanoma cell invasion across human brain endothelium. ECIS data can be mathematically modelled to assess which component of the endothelial paracellular and basolateral barriers is being affected and when. Our results reveal that a range of human melanoma cells can mediate disruption of human brain endothelium, primarily involving the paracellular route, as demonstrated by ECIS. The sensitivity of ECIS also reveals that the paracellular barrier weakens within 30&ndash 60 min of the melanoma cells being added to the apical face of the endothelial cells. Imaging reveals pronounced localisation of the melanoma cells at the paracellular junctions consistent with paracellular migration. Time-lapse imaging further reveals junctional opening and disruption of the endothelial monolayer by the invasive melanoma cells all within several hours. We suggest that the ability of ECIS to resolve changes to barrier integrity in real time, and to determine the route of migration, provides a powerful tool for future studies investigating the key molecules involved in the invasive process of cancer cells. |
Databáze: | OpenAIRE |
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