Pancreatic cancer (PaCa) is the fourth most common cancer worldwide and among the deadliest cancers in Australia. The only potential curative treatment is pancreaticoduodenectomy but unfortunately, approximately only 15%- 20% of patients are suitable for surgery at the time of diagnosis. Even after this intervention, only 10% - 20% of patients stand a chance for a 5-year survival. Currently, the only approved PaCa biomarker is serum carbohydrate antigen 19-9 (CA 19-9), which has 87% specificity and 80% sensitivity, and is used as a prognostic biomarker during therapy, pre- and post-operatively. Due to a deficiency in the Lea-b genetic locus, 5% - 10% of the population will turn up with false negative results when tested, thus rendering CA 19-9 ineffective as a PDAC biomarker.
Exosomes are 30-100nm in diameter, lipid bilayer membrane microvesicles secreted both from normal and malignant cells. Among others, PaCa cell-derived exosomes have demonstrated the ability to trigger the formation of a pre-metastatic niche in the liver. So far, there has been little research has been done as for the lipid composition of exosomes. Our group has always had a strong interest in lysolipids and in particularly lysophosphatidylinositol. In the past we demonstrated that LPI acts as a mitogen in k-ras transformed cells and that the LPI/GPR55 interaction is pivotal in the maintenance of an autocrine loop, which sustains prostate cancer cell proliferation. We identified a novel role for the receptor GPR55 and LPI as a key regulator of cancer cell proliferation and anchorage-independent growth. We have also managed to identify a similar loop in pancreatic cancer cells and we are now looking for a specific lipid signature in PaCa that can be used objectively as a novel biomarker. Our work involves a lipidomic profiling of multiple PaCa cell lines exosomes, with a special focus on lysolipid species.