Abstract 1021: Lipidomic analysis: a powerful tool for evaluating lipid metabolism in cultured cancer cells

Lipids have numerous functions in biological processes, structural as well as regulatory. Cancer cells show differences from healthy normal cells in their metabolism, including lipid metabolism, which contribute to their survival and growth. Overexpression of fatty acid synthase (FASN) is commonly observed in cancer cells and there is also evidence of other lipid pathways being changed in tumor cells. The general aim of this project is to establish a lipidomic based UPLC-QToF method for evaluation of lipid composition in cultured cells of normal and cancerous origin using electrospray quadrupole traveling wave ion mobility Q-ToF mass spectrometry. Cell lines were selected based on their lipid metabolism, including three breast cancer cell lines: SK-Br-3 (overexpresses FASN), T47D (TP53-mutated), MCF7 (estrogen receptor-positive); and one pancreatic cancer cell line, ASPC-1(overexpresses 5-and 12-lipoxygenases). Furthermore, we analyzed the immortalized breast epithelial stem cell line D492 along with its subline, D492M, that has undergone epithelial to mesenchymal transition (EMT). Principal component analysis (PCA) revealed distinct differences in lipid composition between all the cell lines tested, each cell line showed a clear cluster of lipid components and patterns that were reproducible between experiments. The Sk-Br-3 was most clearly separated from the other two breast cancer cell lines. Further analysis revealed significant differences in levels of phosphocholins (PC) that are elevated in Sk-Br-3compared to other cell lines. Further investigations of the data have led to identification of certain PC that are different between cell lines. Significant differences were detected in the lipid composition of D492 and D492M. In conclusion, different levels of lipid-synthesizing enzymes are reflected in distinct lipid profiles in breast cancer cells. The observed differences in lipid profiles of the breast epithelial cell line and its mesenchymal-like subline may provide an insight into membrane changes associated with EMT and help evaluate lipidomes of tumor samples from patients in terms of invasive potential. Citation Format: Finnur F. Eiriksson, Manuela Magnusdottir, Skarphedinn Halldorsson, Margret Thorsteinsdottir, Helga M. Ogmundsdottir. Lipidomic analysis: a powerful tool for evaluating lipid metabolism in cultured cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1021.