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Determining the impact of exercise on the initiation of breast cancer skeletal metastasis using pre-clinical models

Project Description

Breast cancer death is mainly due to the effects of the cancer spreading outside the breast tissue and forming secondary tumours (metastases) in other organs. Bone is the most frequent place to which breast cancer spreads, suggesting that this organ provides a specifically, supportive place for breast cancer cells to grow. Bone structure is constantly altered throughout life and especially in response to exercise. Such changes may alter the ability of tumour cells to relocate to the bone and their capacity for growth there. In this project, we will use unique methods developed in our laboratory for controlled mechanical loading of the bone (mimicking exercise) and state-of-the art cancer cell imaging techniques (i.e. multiphoton microscopy) in experimental animal models, to investigate how exercise affects the frequency of breast cancer spread to the skeleton. Interactions between tumour cells and resident bone cells will be examined using immunohistochemistry. Various loading regimens and other translatable approaches to exercise such as treadmills and low-magnitude high-frequency vibration platform will also be adopted to further determine the relationship between exercise and the development of breast cancer bone metastasis. Successful delivery of this project, in the short term, could provide valuable information and promote the awareness, to both public and patients with breast cancer, concerning management of physical exercise and its impact on the secondary spread of breast to bone. In the long term, this proposal could lead to design of personalized regimens of physical exercises to prevent and treat breast cancer spreading to bone in patients with different stages of disease. The study will also reveal mechanisms responsible for the initiation of cancer bone metastases and could result in identifying new drug targets for this deadly disease.

The proposed project will be carried out in the Department of Oncology & Metabolism, The University of Sheffield, UK. Sheffield offers a unique combination of infrastructure and expertise for the planned project that is not available elsewhere in the UK. The University of Sheffield is a Centre of Excellence for musculoskeletal research, which means that there are unique and unrivalled facilities in Sheffield for carrying out studies in the area of bone oncology which the University has committed to continuously support and expand. This will warrant students who are interested in this project to acquire special techniques and skills in bone oncology and bone biology, as well as a broad spectrum of techniques in the fields of cancer biology, cell and molecular biology, biochemistry, and immunology.

Funding Notes

This project is open for self-funded students.

Eligibility Requirements

Talented and motivated applicants are expected to hold a Master’s degree in Cancer Biology or a related discipline, and/or Bachelor’s degree with good marks. The applicants are also expected to have experience in working with experimental animals and good communication skills in English.

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