Chemical profiling of surviving cancer cells using ToF-SIMS and MCR analysis discriminates cell components

Abstract

Cancer cells survive treatment through mechanisms that remain unclear. This study investigates the chemical changes that occur in cancer cells after treatment, focusing on lipid metabolism as a potential marker for survival and resistance. Using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and advanced multivariate statistical analysis, we compared the chemical profiles of untreated and surviving cancer cells. Region-of-Interest (ROI) analysis revealed distinct differences in the lipid compartments, with surviving cancer cells showing significant accumulation of lipid droplets. While Principal Component Analysis (PCA) was able to differentiate the chemistry of untreated and surviving cancer cells as well as their cellular components, Multivariate Curve Resolution (MCR) provided a clearer and more detailed distinction, enabling the identification of specific cellular features such as the cytoplasm, nucleus, and lipid droplets within the surviving cells. The separation of the chemistry in nucleus and lipid droplets emphasizes the effectiveness in complex spectral analysis. Furthermore, the ability to map the distribution of lipid droplets in surviving cells can advance our understanding of how these structures contribute to cancer cell survival during treatment. The study highlights the importance of lipid droplets as potential biomarkers for cancer cell adaptation and survival post-treatment, with implications for developing new therapeutic strategies.