Can stress facilitate breast cancer metastasis to the bone?

The importance of stress in breast cancer progression is recognized. However, there are few studies on the mechanisms by which stress hormones impact spread to the bone. We have previously shown that stress hormones, e.g. cortisol can facilitate metastasis to the lung. However, the interplay between stress and bone metastasis is yet to be established. With over 70% of advanced breast cancer cases involving metastasis to the bone and currently there are no cures, research into the mechanisms are sorely needed. We hypothesize that cortisol will facilitate breast cancer metastasis to the bone through enhancing the expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) which drives the formation of bone-resorbing osteoclasts. To test this hypothesis, we will first characterize the mechanism whereby stress hormones release RANKL from 2 breast cancer cell lines. We will next assess if cortisol promotes release of RANKL in freshly isolated murine osteoclasts. Osteoclasts will be co-cultured with breast cancer cells in the presence of stress hormones and markers of metastasis will be measured as well as RANKL expression (ELISA/Western blotting) and the differentiation and bone-resorbing potential of the osteoclasts (histological TRAP labelling). We will also use In vivo models of metastatic breast cancer in the presence or absence of restraint stress and examine the bone microarchitecture and metastases formation by microCT (collaboration with the Royal Veterinary College). Such findings will provide valuable insight for patients and clinicians that stress is an important determinant in bone metastasis. This would then be an avenue for intervention for breast or other cancers which spread to the bone. The successful candidate will work with a multidisciplinary team of supervisors and this project uses cutting-edge technologies with the potential for clinical impact. Additional training in scientific writing, science communication, project management and teamwork will be provided formally through postdoctoral training programmes at the University of Brighton. This is a three-year, full time position funded by the University of Brighton and starting in October 2021. The studentship will provide UK/EU tuition fees, a stipend in line with the RCUK rate and a budget for research expenses and training.