Characterizing ex vivo models for studying lipid metabolism in triple negative breast cancer

Lipid metabolism drives cancer progression but is difficult to model using conventional methods. In vivo models provide access to circulating lipids, but are costly and low throughput, while in vitro models lack sufficient lipid availability in culture media. Here, we evaluate the chick chorioallantoic membrane (CAM) patient-derived xenograft (PDX) and tissue slice models as ex vivo cancer models of lipid metabolism in triple-negative breast cancer (TNBC) over a 9-day incubation period using lipidomics analysis. Differences in the TNBC tumour lipidome were driven by inherent differences between primary and metastatic tumours, then by ex vivo model. Ether-linked phosphatidylcholine and phosphatidylcholine lipids accumulated in CAM xenografts from primary and metastatic TNBC tumours (q < 0.05) but were unchanged in ex vivo tumour slices. Conversely, elevated triacylglycerol, sphingomyelin, and phosphatidylglycerol lipids were prominent in ex vivo tumour slices from primary and metastatic TNBC models when compared to CAM-PDX. Cryopreserved tumour fragments were successfully reanimated, demonstrating a similar lipidome profile to freshly engrafted TNBC tumour fragments in the CAM-PDX model. Hierarchical clustering of total saponifiable fatty acids revealed ex vivo model dependent differences, suggesting that the lipids availability to the tumour environment may influence fatty acyl composition, but not the distribution of esterified lipids. Our findings define the time-dependent lipid subclass accumulation in CAM-PDX and ex vivo tumour slice models, and highlight their utility in the study of the TNBC lipidome.