Abstract
Prostate cancer (PCa) is the most common cancer and second leading cause of cancerrelated deaths in men in the UK. Approximately 40% of patients diagnosed with advancedprostate cancer eventually develop metastasis, being the leading cause of prostateassociated deaths. Rho GTPases are known to contribute to cancer development and
progression, including tumour growth, invasion and metastasis, as they control a variety of
signalling pathways involved in cell migration and proliferation.
RhoH is an atypical Rho GTPase highly expressed in haematopoietic cells and has been
shown to regulate T-cell receptor (TCR) signalling. However, RhoH was also found to be
expressed in a variety of cancer cells, including prostate cancer cell lines, and has been
shown to increase migration in PC3 prostate cancer cells. This study aims to investigate the
role of RhoH in prostate cancer spheroids using PC3 and DU145 prostate cancer cell lines.
Growth assays were performed to determine the conditions that support PC3 and DU145
spheroids, which showed that foetal calf serum (FCS) is essential for spheroid growth and
increasing the concentrations of FCS improves spheroid growth over time. PC3 and DU145
cell lines expressing GFP-RhoH were generated and used to determine whether RhoH
affected spheroid growth, shape and/or invasion. GFP-RhoH expression was found to
decrease PC3 and DU145 spheroid cross-sectional area and increase circularity, implicating
a role of RhoH in PC3 and DU145 spheroid growth and shape, although this was dependent
on the growth conditions. From the spheroid images acquired, hepatocyte growth factor
(HGF) appeared to stimulate cell protrusions in PC3 and DU145 spheroids, confirming the
important role of HGF in PCa migration and invasion in 2D and 3D. However, the
mechanisms by which RhoH affects PCa cell migration or spheroid growth or shape remains
to be investigated
| Date of Award | 2 Dec 2021 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Anne J Ridley (Supervisor) |