Poster Presentation 30th Lorne Cancer Conference 2018

Modelling the development of Barrett’s oesophagus and oesophageal adenocarcinoma (#174)

Elhadi Iich 1 , Nicholas Clemons 1 , Wayne Phillips 1
  1. Peter MacCallum cancer centre, Melbourne, ACT, Australia

Barrett’s oesophagus (BO) is a pre-neoplastic condition which arises at the distal end of the oesophagus and is characterized by changes from a normal squamous epithelium to a metaplastic columnar gastro-intestinal epithelium. The columnar epithelium is composed of a mosaic of cells found both in the stomach and intestines such as mucinous cells and goblet cells respectively.

Patients suffering from BO have increased chances of developing oesophageal adenocarcinoma (OAC). OAC has been increasing over the past 40 years while patients with OAC have abysmal 5 year survival. Importantly, all treatments employed so far have failed to stop the rise in incidence. These trends require a more fundamental understanding of the lesion’s initiation and pathobiology. One of the main questions regarding Barrett’s oesophagus is the cell of origin.

Many studies have been performed to identify and validate the cell of origin for Barrett’s. However, consensus has been lacking. Three dominating hypotheses seem to prevail as to what the potential cell(s) source(s) of Barrett’s is (are): 1) Stem cells from the (supra)basal layer of the squamous epithelium could acquire a columnar and metaplastic phenotype upon stimulation with bile and acid. 2) Progenitors from the submucosal glands (SMGs) underneath the squamous epithelium which are not found in mice or rats could provide a source of cells able to undergo metaplastic adaptation to the same stimulations. 3)  Stem cells from the gastric cardia in the stomach or squamo-columnar junction could upon progressive erosion of the squamous epithelium migrate up the oesophagus and replace the damaged squamous epithelium.

A small number of studies have alluded to the contribution of SMGs in the development of BO; however their contribution to BO has never been appropriately shown or studied. To this end, we are developing appropriate culture systems of potential SMGs stem/progenitor cells to determine their potential role in the development of BO.