MSACL 2026 Abstract

Rapid Screening and Spatial Lipidomics Reveal Chemotherapy-Induced Phospholipidosis and Lipid Metabolic Reprogramming in Ovarian Cancer

Stefania Maneta-Stavrakaki (1), Maria Paraskevaidi (2), Erika Dorado (1), Samantha Hardman (1), Liying Wan (1), Duncan Roberts (1), Apostolia Galani (2), Wangxing Guo (1), Laura Ellis (2), Robbie Murray (3), Maria Kyrgiou (2), Zoltan Takats (1),(4)
(1) Division of Systems Medicine, Department of Metabolism Digestion and Reproduction, Imperial College London, UK (2) Institute of Reproductive and Developmental Biology, Department of Metabolism Digestion and Reproduction, Imperial College London, UK (3) Department of Physics, Imperial College London, UK (4) University of Regensburg, Regensburg, Germany

Stefania Maneta-Stavrakaki, BSc, MSc, PhD (Presenter) Imperial College London

Presenter Bio: I obtained a BSc in Chemistry from the University of Athens, followed by an MSc in Analytical Chemistry from King’s College London, mainly focused in Mass Spectrometry. I then worked as an Analytical Scientist at GSK. I completed my PhD degree in March 2022, in analytical chemistry, with specialisation in the real-time analysis of living cells using Laser Desorption Rapid Evaporative Ionisation Mass Spectrometry (LD-REIMS). I am currently funded by the CRUK Rosetta Grand Challenge and the Convergence Science Centre to study colorectal and head and neck cancers using cell lines and patient derived organoids.

Relevant Financial Disclosures (within past 24 months, reported on Apr 23, 2026) No relevant financial relationship(s) to disclose.

INTRODUCTION:
Ovarian cancer remains the most lethal gynaecological malignancy, with high recurrence rates driven by the development of resistance to platinum-based chemotherapy. Lipid metabolic reprogramming is increasingly recognised as a key mechanism underpinning tumour adaptation and drug resistance; however, comprehensive characterisation across in vitro models and clinical samples remains challenging due to biological heterogeneity and reliance on labour-intensive workflows.
Here, we apply complementary ambient ionisation mass spectrometry techniques – Desorption Electrospray Ionisation (DESI) and Laser Desorption-Rapid Evaporative Ionisation Mass Spectrometry (LD-REIMS) – to enable preparation-free, spatially resolved, and high-throughput lipidomic profiling of ovarian cancer cells, tissues, and patient biofluids. This integrated approach allows direct linkage of mechanistic in vitro findings with clinically relevant lipidomic phenotypes.

METHODS:
The ovarian cancer cell line A2780 was exposed to increasing concentrations of cisplatin and carboplatin to generate chemoresistant clones. Drug-sensitive and resistant cells were analysed directly on chamber slides using DESI-MS and LD-REIMS with minimal sample preparation.
DESI mass spectrometry imaging (DESI-MSI) was performed at 25 × 25 µm² spatial resolution on fresh-frozen ovarian cancer tissue sections, including 48 primary and 18 samples collected following platinum-based chemotherapy. Selected regions of interest were further analysed using higher-resolution LD-REIMS imaging (5 × 5 µm²). Histological annotation was performed on adjacent sections.
In parallel, high-throughput, preparation-free LD-REIMS and DESI-MS screening was conducted on matched pre- and post-treatment plasma samples from 21 ovarian cancer patients.

RESULTS:
Our study reveals a progressive shift in the lipidomic profile of ovarian cancer cells with increasing cisplatin and carboplatin concentrations and levels of resistance. Optical imaging revealed significant morphological alterations in resistant cells, including changes in the plasma membrane and enhanced cellular adhesion. Notably, the formation of intracellular lamellar/lysosomal bodies was also observed, indicating drug-induced phospholipidosis, an established phenomenon characterised by lysosomal phospholipid accumulation, typically caused by cationic amphiphilic drugs.

Although platinum-based chemotherapy agents, including cisplatin, carboplatin, and oxaliplatin, are not typically associated with phospholipidosis due to their lack of cationic and lipophilic properties – both of which are required to disrupt phospholipid metabolism and promote lysosomal accumulation – our DESI-MS screening data revealed a significant increase in lysosomal bis(monoacylglycerol)phosphate (BMP) lipids. Specifically, BMP(40:7), BMP(44:11), and BMP(44:12) were elevated (>2-fold) in resistant clones treated with 5 and 10 µM cisplatin and 15 and 25 µM carboplatin compared to treatment-naïve and sensitive cells. These BMP lipids are recognised biomarkers of phospholipidosis, suggesting a previously unreported lipid reprogramming phenomenon in platinum resistance.

Structural confirmation of BMP lipids and their distinction from isomeric phosphatidylglycerol (PG) lipids were achieved using LC-MS/MS and authentic standards. Preliminary DESI mass spectrometry imaging (DESI-MSI) of high-grade serous ovarian carcinoma tissues from patients following platinum-based chemotherapy confirmed the presence of BMP(40:8), BMP(40:7), and BMP(44:12) within tumour regions.

Finally, high-throughput LD-REIMS and DESI-MS analysis of matched pre- and post-treatment plasma samples from 21 ovarian cancer patients demonstrated a significant increase in lipid content, including fatty acids, phosphatidylethanolamine (PE), ceramides (Cer), and sphingomyelin (SM) species, in post-treatment samples, further indicating treatment-associated lipidomic reprogramming.

CONCLUSION:
This study demonstrates that ambient ionisation mass spectrometry enables spatially resolved, rapid, preparation-free, multi-scale lipidomic profiling across cells, tissues, and biofluids. Our findings reveal a previously unreported association between platinum-based chemotherapy and phospholipidosis, characterised by the accumulation of lysosomal BMP lipids.

Our results highlight substantial lipid alterations in cisplatin- and carboplatin-resistant ovarian cancer cells, including morphological changes and upregulation of lysosomal lipids directly linked to drug-induced phospholipidosis – a phenomenon characterised by intracellular accumulation of phospholipids within lamellar bodies, most likely resulting from impaired lysosomal phospholipid metabolism.

These findings suggest that alterations in lipid metabolism and phospholipidosis may contribute to platinum resistance, as well as platinum-induced organ toxicity, such as hepatotoxicity, providing new opportunities for therapeutic intervention and biomarker discovery in ovarian cancer.