SCIENCE: University of Leeds co-funded PhD project
Published 26 Jan 2018
Breast Cancer UK is pleased to announce an award of £45,000 to Dr James Thorne that will go towards funding a 3 year PhD project to investigate how oxysterols promote breast cancer progression (1). The studentship will be co-funded by the University of Leeds.
Oxysterols (2) are a group of chemicals which may be associated with an increased risk of breast cancer, its recurrence and spread. In a pilot project funded by Breast Cancer UK, Dr Thorne and his collaborator Dr Hanne Røberg-Larsen (from the University of Oslo) developed a method to measure multiple oxysterols in very small samples of breast tissue.
The new research will expand on this work and investigate whether different oxysterols are present in different tumour types and explore if individual oxysterols could predict breast cancer relapse.
The PhD student will also investigate which cells are the source of oxysterols by measuring oxysterols in different cell types found in breast cancers. Most importantly for BCUK, dietary factors that prevent oxysterol signalling will be investigated, to see if they could impair the cellular pathways that lead to breast cancer recurrence.
Many breast cancers are thought to be preventable through diet and lifestyle choices, but the mechanisms for prevention remain unclear. Obesity and elevated cholesterol are risk factors for breast cancer initiation and progression, but exact mechanisms are not understood fully. Cholesterol levels are influenced by a variety of dietary and lifestyle factors, and high LDL-cholesterol has been linked to failure of cancer therapy.
The cholesterol metabolic pathway is altered in breast cancer, leading to increased production of products, known as oxysterols. It is thought certain oxysterols promote tumour progression. Non-cancer host cells such as fat cells (adipocytes), support cells (fibroblasts) and immune system cells (macrophages) convert cholesterol into oxysterols and the presence of these non-cancer cell types in the tumour micro-environment (3) has been linked to cancer spread and drug-resistance.
This project will explore the hypothesis that oxysterols, released by non-cancer host cells into the tumour micro-environment, are taken up by adjacent breast cancer cells, eventually leading to chemotherapy resistance and tumour spread. As oxysterols may promote tumour progression, interventions which interfere with their production may prevent breast cancer relapse. This work will also investigate whether a dietary intervention can alter oxysterols produced by host cells, thereby preventing breast cancer recurrence.
For details of Dr Thorne’s previous research funded by BCUK see here.
1. Breast Cancer UK awarded a grant of £45,000 to Dr James Thorne (PI) and Dr Hanne Røberg-Larsen (University of Oslo) to support a PhD studentship, to investigate “Oxysterols as functional biomarkers of TNBC relapse”. The University of Leeds will also contribute £45,000 to support the studentship.
2. Oxysterols are produced by the oxidation of cholesterol. This can happen when food is prepared using high temperature methods such as frying or through enzyme reactions in the body. As such, oxysterols occur in the body naturally and through dietary intake.
3. The tumour micro-environment describes the whole of the tumour, including all the non-cancerous cells that have invaded or have been enveloped by the tumour. These include fibroblasts (which provide support for other cells), macrophages (part of the immune system), adipocytes (fat storage cells) as well as the vasculature that supplies the tumour with nutrients and oxygen through the blood supply. It also includes the proteins, metabolites and the space in between cells. All together this mixture of different cell types support the growth of the cancer cells.