@article{ea914f08b47b4e1687a2a6d1582be992,
title = "Metabolic profiling of colorectal cancer organoids: A comparison between high-resolution magic angle spinning magnetic resonance spectroscopy and solution nuclear magnetic resonance spectroscopy of polar extracts",
abstract = "Patient-derived cancer cells cultured in vitro are a cornerstone of cancer metabolism research. More recently, the introduction of organoids has provided the research community with a more versatile model system. Physiological structure and organization of the cell source tissue are maintained in organoids, representing a closer link to in vivo tumor models. High-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) is a commonly applied analytical approach for metabolic profiling of intact tissue, but its use has not been reported for organoids. The aim of the current work was to compare the performance of HR MAS MRS and extraction-based nuclear magnetic resonance (NMR) in metabolic profiling of wild-type and tumor progression organoids (TPOs) from human colon cancer, and further to investigate how the sequentially increased genetic alterations of the TPOs affect the metabolic profile. Sixteen metabolites were reliably identified and quantified both in spectra based on NMR of extracts and HR MAS MRS of intact organoids. The metabolite concentrations from the two approaches were highly correlated (r = 0.94), and both approaches were able to capture the systematic changes in metabolic features introduced by the genetic alterations characteristic of colorectal cancer progression (e.g., increased levels of lactate and decreased levels of myo-inositol and phosphocholine with an increasing number of mutations). The current work highlights that HR MAS MRS is a well-suited method for metabolic profiling of intact organoids, with the additional benefit that the nondestructive nature of HR MAS enables subsequent recovery of the organoids for further analyses based on nucleic acids or proteins.",
keywords = "colorectal cancer, HR MAS MRS, lactate, myo-inositol, NMR, organoids, phosphocholine, tumor progression organoids",
author = "{van der Kemp}, {W J M} and Grinde, {M T} and Malvik, {J O} and {van Laarhoven}, {H W M} and Prompers, {J J} and Klomp, {D W J} and Burgering, {B M T} and Bathen, {T F} and Moestue, {S A}",
note = "Funding Information: Research reported in this publication was funded by EU Horizon 2020, FETOPEN 2016–2017 Grant number: 801075; NICI. Experiments at the 600 MHz instrument for solution NMR were supported by uNMR‐NL, the National Roadmap Large‐Scale NMR Facility of the Netherlands (NWO grant 184.032.207). The HRMAS MRS analyses were performed at the MR Core Facility, Norwegian University of Science and Technology (NTNU). MR core facility is funded by the Faculty of Medicine at NTNU and Central Norway Regional Health Authority. Funding Information: Experiments at the 600 MHz instrument for solution NMR were supported by uNMR-NL, the National Roadmap Large-Scale NMR Facility of the Netherlands (NWO grant 184.032.207). The authors are indebted to I. Verlaan-Klink, M. L. Ludikhuize, M. J. Rodriguez-Colman, and M. Meerlo for advice on organoid culturing and providing starting batches of the organoids. The HR MAS MRS analyses were performed at the MR Core Facility, Norwegian University of Science and Technology (NTNU). The MR core facility is funded by the Faculty of Medicine at NTNU and Central Norway Regional Health Authority. Funding Information: Experiments at the 600 MHz instrument for solution NMR were supported by uNMR‐NL, the National Roadmap Large‐Scale NMR Facility of the Netherlands (NWO grant 184.032.207). The authors are indebted to I. Verlaan‐Klink, M. L. Ludikhuize, M. J. Rodriguez‐Colman, and M. Meerlo for advice on organoid culturing and providing starting batches of the organoids. The HR MAS MRS analyses were performed at the MR Core Facility, Norwegian University of Science and Technology (NTNU). The MR core facility is funded by the Faculty of Medicine at NTNU and Central Norway Regional Health Authority. Publisher Copyright: {\textcopyright} 2022 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.",
year = "2023",
month = apr,
doi = "10.1002/nbm.4882",
language = "English",
volume = "36",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley & Sons Inc.",
number = "4",
}