The expression of CCR7 was evaluated in different cancer cell lines by using
flow cytometry, western blot, Immunofluorescence and immunohistochemistry.
We showed for the selected cell lines that the expression is maintained in cells
grown as spheroids, and xenoplanted in mice. Furthermore, we showed the
expression of CCR7 correlates with stage of the disease in patient derived head
and neck cancer tissue. We also showed that expression of CCR7 in cancer cell
lines correlates with migratory aptitude towards CCL21 in a scratch assay,
Boyden chamber assay and spheroid invasion assay.
We then showed that the expression of CCR7 is elevated under serum
starvation and under hypoxia in cancer cell lines grown as monolayers and as
spheroids; and that there is a correlation between hypoxia and CCR7
expression in spheroids, xenografted cells and clinical cancer tissue. However,
we found that in cell line OSC-19, the increase in the expression of CCR7 did
not correlate to increased migration. Our investigations following this
observation showed that whilst hypoxia increases the expression of CCR7, it
concurrently causes a decrease in reactive oxygen species (ROS) which
strongly abrogates migratory aptitude in OSC-19, resulting in an overall loss of
migration in OSC-19 cells.
In addition, we characterised OSC-19 as a suitable model to evaluate small
molecule CCR7 antagonists using a number of different assays. In particular,
we showed that ICT13069 antagonised response of this cell line across a
number of drivers of malignancy such as migration, invasion in 2D and 3D
models. / Zarqa University / The full text was made available at the end of the embargo, 3rd December 2019
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/15100 |
| Date | January 2017 |
| Creators | Basheer, Haneen A. |
| Contributors | Afarinkia, Kamyar, Vinader, Victoria |
| Publisher | University of Bradford, Institute of Cancer Therapeutics |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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