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

ABSTRACT:

Lipid metabolism drives cancer progression but is difficult to model using conventional methods. In vivo models provide 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) xenograft and tissue slice models over a 9-day incubation period as ex vivo cancer models of lipid metabolism in triple-negative breast cancer (TNBC) 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 (PC-O) and PC lipids accumulated in CAM xenografts from primary and metastatic TNBC tumours (q < 0.05) but were unchanged in ex vivo tumour slices. Conversely, elevated sphingomyelin (SM) and triacylglycerol (TG) lipids were prominent in ex vivo tumour slices from primary and metastatic TNBC models when compared to CAM xenograft samples. Cryopreserved tumour fragments were successfully reanimated, demonstrating a similar lipidome profile to freshly engrafted TNBC tumour fragments in the CAM-PDX model. Total fatty acid analysis revealed ex vivo model dependent differences, suggesting that the availability of lipids in the tumour microenvironment may influence fatty acyl composition, but not the distribution of esterified lipids. In conclusion, the CAM xenograft and tissue slice models serve as robust and cost-effective tools for studying cancer lipid metabolism over time. This study provides a foundation for characterizing unique lipid alterations that support TNBC tumour growth using ex vivo models.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS13377 | MetaboLights | 2026-07-16

REPOSITORIES: MetaboLights