In Western societies, prostate cancer is the most frequently diagnosed cancer amongst men. Efforts to improve diagnosis and treatment remain a major focus and have been proven beneficial in the approach to localised disease.
However, currently, metastatic disease management still remains palliative. Receptor activator of nuclear kappa B (RANK) has been extensively studied in bone biology and immunology, whilst several links have been made between RANK-positive breast cancer cells and disease progression. Its role in prostate cancer biology remains poorly understood, therefore the aim of this study was to explore the functional role of endogenously produced RANK in metastatic PC-3 prostate cancer cells in isolation and in response to hepatocyte growth factor (HGF).
RANK expression was targeted using hammerhead ribozyme technology in PC-3 prostate cancer cells, and verified by polymerase chain reaction and western blot. A variety of in vitro functional assays were conducted, including cell proliferation and matrix adhesion in the presence of HGF.
Suppression of RANK expression was successfully targeted with anti-RANK hammerhead ribozyme transgenes, as verified by PCR and western blot. Reduced RANK expression resulted in significantly increased PC-3 cell proliferation (p<0.01) and cell-matrix adhesion (p<0.05) compared to control cells.
Previous work into RANK and prostate cancer has focused on its interaction with the bone environment, particularly with regard to its receptor RANK ligand. This study has shown that endogenous RANK expression changes might also influence prostate cancer cell behaviour. Further work is now required to elucidate the signaling pathways involved in these processes.
Anticancer research. 2016 Mar [Epub]
Sioned Owen, Andrew J Sanders, Malcolm D Mason, Wen G Jiang
Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K. Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K., Oncology and Palliative Medicine, Velindre Hospital, Cardiff, U.K., Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.