A 2018/2019 Summer Studentship research project
This research is important because it will increase our understanding of breast cancer and obesity link, and together with ongoing research in MCRG may lead to more effective treatments for early-stage breast cancer patients.
Student: Devon Bull
Supervisors: Dr Elisabeth Phillips, Associate Professor Margaret Currie, Dr Matthew Strother
We are looking for a bright, enthusiastic student to join a multidisciplinary team: The Mackenzie Cancer Research Group (MCRG). The proposed summer-studentship represents an important part of our ongoing research into the role of adipocytes and inflammation in the progression of cancer, but is designed for completion within a 10 week Summer-Studentship.
Systemic inflammation is present in 60% of patients with advanced cancer. Elevated levels of circulating inflammatory cytokines are present in obese (BMI > 30) breast cancer patients, and have been associated with worse breast cancer outcome and prognosis. Breast cancer chemotherapies are processed by enzymes in the liver, and the function of these liver enzymes can be inhibited by inflammatory mediators found in the blood.
In our laboratory, we have shown that human breast cancer cell lines co-cultured with human breast adipocytes (fat cells) are exposed to numerous inflammatory cytokines produced by the adipocytes at a local level. Furthermore, we have used discovery mass-spectrometry to identify a number of protein abundance changes in the breast cancer cells after co-culture with adipocytes. Phosphoglycerate kinase 1 (PGK1) was upregulated by greater than 50% in the breast cancer cell lines cultured with the human breast adipocytes. Increased expression of PGK1 has been identified as a tumour promoter in a number of malignancies, including breast cancer (Sun et al., 2015). The PGK1 enzyme supports ATP generation through the glycolytic pathway and its cellular localization of PGK1 in breast tumours is important in determining its function.
We hypothesise that 1) obese breast cancer patients have elevated levels of systemic inflammation compared to normal weight patients, and that this inflammation remains elevated throughout chemotherapy (potentially hindering the patient’s ability to process chemotherapy medications effectively) and 2) that PGK1 is localised to the cytoplasm in breast cancer cells that are surrounded by a greater number of adipocytes in human breast tumours.
The student will measure markers of systemic inflammation using enzyme linked immunosorbent assays (ELISAs) in serum samples from breast cancer patients taken throughout chemotherapy. If time allows, the student will also assess the localisation of PGK1 expression in human breast cancer tissue sections using IHC and in human breast cancer cell lines using immunofluorescence.