Lipid Heterogeneity Resulting from Fatty Acid Processing in the Human Breast Cancer Microenvironment Identified by GCIB-ToF-SIMS Imaging

Abstract

Breast cancer is an umbrella term used to describe a collection of different diseases with broad inter- and intratumor heterogeneity. Understanding this variation is critical in order to develop, and precisely prescribe, new treatments. Changes in the lipid metabolism of cancerous cells can provide important indications as to the metabolic state of the cells but are difficult to investigate with conventional histological methods. Due to the introduction of new higher energy (40 kV) gas cluster ion beams (GCIBs), time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is now capable of providing information on the distribution of hundreds of molecular species simultaneously on a cellular to subcellular scale. GCIB-ToF-SIMS was used to elucidate changes in lipid composition in nine breast cancer biopsy samples. Improved molecular signal generation by the GCIB produced location-specific information that revealed elevated levels of essential lipids to be related to inflammatory cells in the stroma, while cancerous areas were dominated by nonessential fatty acids and a variety of phosphatidylinositol species with further in-tumor variety arising from decreased desaturase activity. These changes in lipid composition due to different enzyme activity are seemingly independent of oxygen availability and can be linked to favorable cell membrane properties for either proliferation/invasion or drug resistance/survival.

Study of the diacylglycerol composition in the liver and serum of mice with prediabetes and diabetes using MeV TOF-SIMS

“…Our results are in agreement with the TOF-SIMS results obtained on the tissue samples of people suffering from non-alcoholic fatty liver disease [15,32,33]. Additionally, the method is successfully applied to image the location and to quantify a single compound or even a set of compounds in diseases such as colon dysplasia, osteoporosis, breast cancer or chronic obstructive pulmonary disease [34][35][36][37]. To our knowledge, the only work in which TOF-SIMS was used to identify the changes in the lipid composition within mouse tissue (skeletal muscle, liver and adipose tissue) in response to the dietary intake of omega-3 fatty acids was published by Sjovall et al [2].…”

Biomedical surface analysis: Evolution and future directions (Review)

“…It can also be used to identify different regions (tumor, stroma, necrotic, etc.) of breast tissue sections as well as the distribution of key lipids and fatty acids 119–121 . These results provide insight into the metabolic state of cells in the tissue sections and the effectiveness of various regimes used to treat the cancer tumors.…”

Mass Spectrometry for Single-Cell Analysis

“…It has been noted that SIMS is a relatively tough ionization technique, and the molecular weight of the ionized species occurs in the narrow weight range. Therefore, it is well suitable for the study of lipids, small-molecule metabolites, molecular fragments, and elements (Angerer et al 2016;Aoyagi et al 2015;Taylor et al 2015;Voras et al 2015). Based on the ion intensity and quantity of the surface damage via an ion beam, SIMS is categorized into two different (static and dynamic) modes.…”