Investigating the effects of mesenchymal stem cells and exercise on breast cancer progression in vitro

• Main Author: Marie-Juliet Brown
• Format: Dissertation
• Language: English
• Subjects: Breast cancer; exercise; exercise oncology; in vitro; mesenchymal stem cells; Sports science and exercise not elsewhere classified
• DOI: 10.26174/thesis.lboro.23548308.v1

Breast cancer is the most prevalent cancer in women worldwide. Whilst overall breast cancer (BC) survival rates have improved, metastatic breast cancers remain fatal.  Metastatic breast cancers are extremely complex diseases, generated by a plethora of multi-faceted processes and interactions that results in the metastatic dissemination of cancer cells. Critical to the pathophysiology of cancer, the tumour microenvironment is made up of tumour cells as well as various non-malignant stromal and immune cells. Critically, mesenchymal stem cells (MSCs) are a population of stromal cells that are found in most tumours. They have been widely implicated in breast cancer development and progression, but their role in the development of this disease remains discordant; research demonstrates that MSCs display both tumour-promoting and tumour-suppressive effects. Exercise oncology is a rapidly emerging field and physical activity has long been shown to reduce the risk of many diseases, including breast cancer. However, evidence supports the notion that physical activity not only reduces the risk of developing breast cancer but can also positively affect the progression of breast cancer. The studies described in this thesis investigated the role MSCs play in BC progression in vitro, as well as the role exercise plays in BC progression in vitro; two factors which are combined in the final chapter of this thesis.  Chapter II describes the investigation of the effects of altering glucose concentration and the source of foetal bovine serum (FBS) on the growth of two breast cancer cell lines (T47D and MDA-MB-231) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to determine successful conditions to enable their co-culture in 3D tumour spheroid models. The results herein demonstrated that FBS source had a significant effect on the growth parameters measured in this study. Three-dimensional tumour spheroids were then generated to create physiologically relevant models of BC that could be used to study the influence of MSCs on BC in vitro.  Results demonstrated that co-culture of hBM-MSCs and MDA-MB-231 cells dramatically reduced the invasiveness of both cell lines (P = 0.001) in vitro. Chapter III contains a systematic review and meta-analysis that identified and summarised existing literature on the effects of human mesenchymal stem cells (hMSCs) from different sources on the migration of breast cancer cells (BCCs) in vitro. This study determined the direction