FL 04 - Lipidome of extracellular vesicles in hypoxic pancreatic cancer
FL 04 - Lipidome of extracellular vesicles in hypoxic pancreatic cancer
Pancreatic cancer (PC) has the worst prognosis among all cancers. It remains asymptomatic in early stages, making early diagnosis challenging with established screening methods. Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of PCs and is predominantly diagnosed at an advanced stage, resulting in the lowest five-year survival rate (7%) [1]. Several types of blood tests are considered for PDAC screening [2], such as carbohydrate antigen (CA) 19-9, either alone or in combination with other blood proteins. However, magnetic resonance imaging, computed tomography, endoscopic ultrasound, and positron emission tomography remain the most reliable tools for PC diagnosis in clinical practice. Circulating tumour DNA and extracellular vesicles (EVs) are emerging as promising tools for the early diagnosis of PDAC. This study focuses on the lipidomic profiling of EVs, with particular attention to exosomes lipid bilayer vesicles secreted by cells into the extracellular space. EVs are classified as exosomes (30–150 nm), microvesicles (50-1000 nm), and apoptotic bodies (≥500 nm) [3]. By analysing lipid composition and concentration in exosomes, we aim to identify novel circulating biomarkers for early PDAC detection. Such biomarkers could offer a significant improvement over current diagnostic strategies, contributing to correct prognosis and treatment outcomes. The study has been performed on samples obtained from cellular line PANC1 (immortalized PDAC cells), collected and filtered through 100kDa MWCO filters. A total exosome isolation solution was added and left to react overnight and then vesicles were collected through exospin columns. Lipid extraction following the Bligh & Dyer protocol was performed on cell pellet and the samples were analysed by hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization high-resolution Fourier-transform mass spectrometry (ESI FTMS). In this contribution, preliminary results on the lipidome characterization of EV from PANC1 grown in normoxia and hypoxia conditions are reported. Moreover, the characterization of oxysterols (OS) revealed some interesting differences between control and pancreatic cell lines in terms of OS that are known to be related to oxidative stress condition. This work is supported by project “LIpidome of extracellular VEscicles in hypoxic pancreatic cancer” acronimo “LIVE” CUP - H93C24000620006, Bando a cascata emanato dallo Spoke 6 del Tuscany Health Ecosystem a valere sulle risorse del PNRR, M4C2 - NEXTGENERATIONEU.
American Cancer Society, Pancreatic Cancer Early Detection, Diagnosis, and Staging. https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging.html. Accessed on 28 March 2025.
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