Comprehensive Sterolomics: Expanding Analytical Horizons in Sterol and Oxysterol Metabolism for Cancer Progression

• Applicant: Dr. Sven Meckelmann
• Subject Area: Analytical Chemistry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 463367585

Cholesterol is probably the most abundant and extensively studied lipid in the last decades. However, the analysis of the whole biosynthesis is challenging because of the structural similarity, interferences by matrix compounds or the high concentration of cholesterol, the sensitivity as well as the reproducibility of existing method. Therefore, a heart-cut LC-LC method using triple quadrupole detection was developed to overcome these obstacles in a previous project with the title "A novel target approach to characterize the Biosynthesis of Cholesterol in Cancer Cells". It allows analyzing cholesterol and ist biosynthetic precursors in one analysis with high sensitivity and reproducibility. The method was used to characterize sterols in melanoma and pancreas cancer cells indicating an adapted sterol metabolism to promote tumor progression and metastatic properties. However, important downstream metabolites were not in the scope of the project and therefore have not yet been incorporated to investigate oxysterol in one target LC-MS method. The developed LC-LC-MS method showed already promising indications that also oxysterols can be incorporated into the method. This will require some adaptation regarding the i) chromatographic method, ii) mass spectrometry detection, and iii) sample preparation. In the application stage, the method will be applied to study the metastatic progression of melanoma in ist adaptation to the metabolic microenvironment. In addition, statin treatment and dietary effects on the sterol/oxysterol biosynthesis will be investigated to elucidate their effects on cancer development. Together with established non-target lipidomics, this will provide new insights into the lipid metabolism of melanoma cancer during metastasis.

• DFG Programme: Research Grants