dc.contributor.advisor |
Graham, Scott |
|
dc.contributor.author |
Spurling, Dayna Marie |
|
dc.date.accessioned |
2022-10-31T01:37:16Z |
|
dc.date.available |
2022-10-31T01:37:16Z |
|
dc.date.issued |
2022 |
en |
dc.identifier.uri |
https://hdl.handle.net/2292/61736 |
|
dc.description.abstract |
Introduction and Aims: Brain metastasis is the most devastating complication of metastatic
disease, of which melanoma has the highest propensity to invade the brain of any other cancer.
Treatments for brain metastasis are limited due to the tight structure of the blood-brain barrier,
however melanoma cells harbour mechanisms to disrupt the integrity of the cerebral
microvasculature and invade through the endothelial cells. The literature surrounding
melanoma metastasis suggest the cells disrupt the cerebral endothelial cells and secrete prometastatic factors to aid this process, although the extent of which are not fully understood.
This study examines the effects of a non-adherent sub-population released by melanoma cells
in vitro on the integrity of the blood-brain barrier, to further investigate the mechanisms
employed by melanoma cells to extravasate into the brain.
Methods: Electrical Cell-Substrate Impedance Sensing (ECIS) technology was used to assess
the effect of the melanoma-derived subpopulation on the barrier function of human brain
endothelial cells. Imaging techniques such as immunocytochemistry and fluorescent confocal
microscopy were used to visualise the effects of the melanoma material on the integrity of the
endothelium, and detect the mechanism of interaction in 3D. Flow cytometry and fluorescence
activated cell sorting (FACS) were used to analyse the size and density of the material and
distinguish the bioactive material within the sample.
Results: The melanoma material induced disruption of the endothelial barrier at a considerably
higher rate than their parent melanoma line. This disruption was shared between both the
paracellular and basolateral components, suggesting a transcellular route of entry. The
melanoma material rapidly associated with the endothelial cell body, inducing global changes
in cell structure. 3-Dimensional visualisation confirmed endothelial cell uptake of the
melanoma material through a transcellular mechanism.
Discussion: The current literature surrounding melanoma extravasation at the cerebral
endothelium suggests the cells use a paracellular mechanism, and release factors to enhance or
prime metastatic ability. The preliminary results of this study suggest the material produced by
the melanoma cells could be vesicle-like in nature, likely a result of apoptosis or membrane
blebbing, that have independent effects on the integrity of the blood brain barrier, with a
potential role in enhancing melanoma brain metastasis. |
|
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
|
dc.title |
Analysis of melanoma cell material and their effect on the brain endothelial barrier |
|
dc.type |
Thesis |
en |
thesis.degree.discipline |
Biomedical Science |
|
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.date.updated |
2022-09-27T10:10:58Z |
|
dc.rights.holder |
Copyright: the author |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |