Desmoglein-2 as a regulator of pancreatic ductal adenocarcinoma progression

Thesis (PhD(Medical Science))--University of South Australia, 2022. Includes bibliographical references (pages 191-219) Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent type of pancreatic cancer which develops in the exocrine compartment of the pancreas. Over the course of this PhD project, the cell-surface cadherin Desmoglein-2 (DSG2) was identified to be highly expressed in ~85% of PDAC patient samples and that it correlates with poor patient outcome. DSG2 promotes the proliferation, migration, and invasion of PDAC cells and when DSG2 expression is reduced, PDAC tumours in orthotopic xenograft murine models are significantly smaller with reduced metastasis. The delivery of a DSG2-targeting monoclonal antibody into PDAC-tumour bearing mice also resulted in a significant reduction of tumour growth and distant lung metastasis. Protein signalling studies have identified DSG2 to be critical in propagating growth factor-induced cell signalling pathways that promote tumour growth and metastasis.