dc.contributor.author |
Anchan, Akshata |
|
dc.contributor.author |
Finlay, Graeme |
|
dc.contributor.author |
Angel, Catherine E |
|
dc.contributor.author |
Hucklesby, James JW |
|
dc.contributor.author |
Graham, Scott E |
|
dc.coverage.spatial |
Switzerland |
|
dc.date.accessioned |
2022-12-14T03:37:11Z |
|
dc.date.available |
2022-12-14T03:37:11Z |
|
dc.date.issued |
2022-08-19 |
|
dc.identifier.citation |
(2022). Biosensors, 12(8), 660-. |
|
dc.identifier.issn |
2079-6374 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/62149 |
|
dc.description.abstract |
We have previously shown that human melanoma cells rapidly decrease human brain endothelial barrier strength. Our findings showed a fast mechanism of melanoma mediated barrier disruption, which was localised to the paracellular junctions of the brain endothelial cells. Melanoma cells are known to release molecules which cleave the surrounding matrix and allow traversal within and out of their metastatic niche. Enzymatic families, such as matrix metalloproteinases (MMPs) and proteases are heavily implicated in this process and their complex nature in vivo makes them an intriguing family to assess in melanoma metastasis. Herein, we assessed the expression of MMPs and other proteases in melanoma conditioned media. Our results showed evidence of a high expression of MMP-2, but not MMP-1, -3 or -9. Other proteases including Cathepsins D and B were also detected. Recombinant MMP-2 was added to the apical face of brain endothelial cells (hCMVECs), to measure the change in barrier integrity using biosensor technology. Surprisingly, this showed no decrease in barrier strength. The addition of potent MMP inhibitors (batimastat, marimastat, ONO4817) and other protease inhibitors (such as aprotinin, Pefabloc SC and bestatin) to the brain endothelial cells, in the presence of various melanoma lines, showed no reduction in the melanoma mediated barrier disruption. The inhibitors batimastat, Pefabloc SC, antipain and bestatin alone decreased the barrier strength. These results suggest that although some MMPs and proteases are released by melanoma cells, there is no direct evidence that they are substantially involved in the <b>initial</b> melanoma-mediated disruption of the brain endothelium. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
MDPI |
|
dc.relation.ispartofseries |
Biosensors |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Blood-Brain Barrier |
|
dc.subject |
Brain |
|
dc.subject |
Endothelium |
|
dc.subject |
Endothelial Cells |
|
dc.subject |
Humans |
|
dc.subject |
Melanoma |
|
dc.subject |
Peptide Hydrolases |
|
dc.subject |
Matrix Metalloproteinase 2 |
|
dc.subject |
ECIS |
|
dc.subject |
barrier function |
|
dc.subject |
blood–brain barrier |
|
dc.subject |
impedance |
|
dc.subject |
matrix metalloproteinases |
|
dc.subject |
proteases |
|
dc.subject |
xCELLigence |
|
dc.subject |
Clinical Research |
|
dc.subject |
Neurosciences |
|
dc.subject |
Cancer |
|
dc.subject |
0301 Analytical Chemistry |
|
dc.subject |
0601 Biochemistry and Cell Biology |
|
dc.title |
Melanoma Mediated Disruption of Brain Endothelial Barrier Integrity Is Not Prevented by the Inhibition of Matrix Metalloproteinases and Proteases. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.3390/bios12080660 |
|
pubs.issue |
8 |
|
pubs.begin-page |
660 |
|
pubs.volume |
12 |
|
dc.date.updated |
2022-11-19T02:26:27Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
36005056 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/36005056 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
916602 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
pubs.org-id |
Medical Sciences |
|
pubs.org-id |
Molecular Medicine |
|
dc.identifier.eissn |
2079-6374 |
|
dc.identifier.pii |
bios12080660 |
|
pubs.record-created-at-source-date |
2022-11-19 |
|
pubs.online-publication-date |
2022-08-19 |
|