Examining the inflammatory profile of adipose tissue in oesophageal cancer.

Oesophageal adenocarcinoma is one the cancers most closely associated with obesity and has demonstrated a 400% increase over the past 30 years. The reasons for this association is unknown. It is strongly suspected that visceral fat creates an inflammatory process that significantly favours the development of oesophageal cancer and other cancers. The inflammatory profile, visceral and preoteonomic profile present in the visceral fat of patients with oesophageal cancer has not previously been described. Dysregulation of fat metabolism in adipose tissue located adjacent to the oesophagus may contribute to the development of oesophageal cancer. This PhD will seek to better understand the lipid profile, particularly visceral that may be leading to the observed increase susceptibility to oesophageal adenocarcinoma. Objective The objective of this study is to describe the inflammatory profile of adipose tissue in oesophageal cancer and to determine whether specific adipose tissue related lipids (free fatty acids) or proteins contribute to the development of oesophageal adenocarcinoma. Hypothesis Adipose tissue adjacent to oesophageal cancers demonstrate a significantly different inflammatory cell profile that is pro-tumourigenic in genetically susceptible individuals Aims To determine the difference in adipose tissue adjacent and remote from oesophageal cancer in terms of: Immune cell profile, Cytokine secretion, mRNA content of pro- and anti-inflammatory cytokines / chemokines, Secreted products from adipose tissue demonstrating pro-tumourigenic properties Approach: At the time of oesophageal cancer surgery, adipose tissue will be removed from a location immediately in contact with the tumour and at a distant visceral location. Serum will be collected. A control group of age and weight matched subjects will undergo similar analysis. The tissue will be transported to the laboratory and a series of measures undertaken. This will include lipidomic and proteonomic analysis, with incubation of established tumour cell lines in extracted adipose tissue supernatant. Together, these studies will determine the immune cell profile of adipose tissue located in close proximity to the tumour, it’s capacity for inflammatory cytokine secretion and whether the secreted factors a more pro-tumourigenic than factors secreted from adipose tissue located a long way from the tumour.