MS imaging of multicellular tumor spheroids and organoids as an emerging tool for personalized medicine and drug discovery

Abstract

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Proteomic Changes in the Monolayer and Spheroid Melanoma Cell Models of Acquired Resistance to BRAF and MEK1/2 Inhibitors

“…Methods using serial trypsinization techniques have been described to analyze protein changes within the different layers of spheroids . In addition, MS imaging methods such as matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) have been used to record differences in nutrient/metabolite gradients and cellular functions such as glycolysis, ATP metabolism, apoptosis, and proliferation within a corresponding spheroid layer . These techniques reinforce the physiological changes observed in spheroids, such as exponential growth before plateauing and the formation of a necrotic core, as well as greater proportions of cells in the G1 cell cycle arrest in spheroids versus the G2/M phase more likely to be detected in monolayers. , Not only may these techniques provide information on how individual cell layers contribute to overall drug resistance but they are also amenable to studying the permeability of different drugs in a 3D environment …”

Three-Dimensional Mass Spectrometry Imaging Reveals Distributions of Lipids and the Drug Metabolite Associated with the Enhanced Growth of Colon Cancer Cell Spheroids Treated with Triclosan

“…The penetration of drugs and their metabolites into tumor tissues is essential for evaluating the effects of drugs on tumor growth . In order to investigate the distribution of these compounds in tumor tissues, traditional imaging methods such as PET, MRI, and fluorescence imaging (FI) have been used, which either have a low spatial resolution (millimeter level, for example, PET and MRT) or need a time-consuming labeling procedure (e.g., FI) . MALDI-MSI is a label-free imaging technology that provides a better spatial resolution for cancer research .…”

Metabolomics-based mass spectrometry methods to analyze the chemical content of 3D organoid models

“…10 Additionally, Matrigel has several components that can interfere with mass spectrometry (MS) analysis. 11,12 Sample preparation methods to reduce the interference from Matrigel components are discussed in Sections 2.1 and 2.3.…”

“…2). 27 While several reviews covering the use of MS for organoid analysis have been published, 12,[28][29][30] this work focuses on metabolomics measurements in organoids using separation-and imaging-based MS methods. We describe applications beyond cancer research and drug discovery, and present some of the latest research in this rapidly evolving field.…”