Mass Spectrometry Imaging Reveals a Gradient of Cancer-like Metabolic States in the Vicinity of Cancer Not Seen in Morphometric Margins from Microscopy
| Autor: | Taira Kiyota, Isabelle Ferry, Mark Zaidi, Howard J. Ginsberg, James T. Rutka, Lauren Katz, Georgia Gopinath, Chris McIntosh, Siham Amara-Belgadi, Craig Daniels, Fred Fu, Claudia M. Kuzan-Fischer, Arash Zarrine-Afsar, Ahmed Aman, Brad Wouters, Kaitlyn Peters, Trevor D. McKee, Michael Woolman |
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| Rok vydání: | 2021 |
| Předmět: |
Microscopy
Chemistry Spatially resolved 010401 analytical chemistry Cancer Laser Capture Microdissection Lipidome 010402 general chemistry Mass spectrometry medicine.disease 01 natural sciences Mass spectrometry imaging 0104 chemical sciences Analytical Chemistry Mice Tandem Mass Spectrometry Interstitial fluid Neoplasms Biophysics medicine Animals Humans Chromatography Liquid Laser capture microdissection |
| Zdroj: | Analytical Chemistry. 93:4408-4416 |
| ISSN: | 1520-6882 0003-2700 |
| DOI: | 10.1021/acs.analchem.0c04129 |
| Popis: | Spatially resolved ambient mass spectrometry imaging methods have gained popularity to characterize cancer sites and their borders using molecular changes in the lipidome. This utility, however, is predicated on metabolic homogeneity at the border, which would create a sharp molecular transition at the morphometric borders. We subjected murine models of human medulloblastoma brain cancer to mass spectrometry imaging, a technique that provides a direct readout of tissue molecular content in a spatially resolved manner. We discovered a distance-dependent gradient of cancer-like lipid molecule profiles in the brain tissue within 1.2 mm of the cancer border, suggesting that a cancer-like state progresses beyond the histologic border, into the healthy tissue. The results were further corroborated using orthogonal liquid chromatography and mass spectrometry (LC-MS) analysis of selected tissue regions subjected to laser capture microdissection. LC-MS/MS analysis for robust identification of the affected molecules implied changes in a number of different lipid classes, some of which are metabolized from the essential docosahexaenoic fatty acid (DHA) present in the interstitial fluid. Metabolic molecular borders are thus not as sharp as morphometric borders, and mass spectrometry imaging can reveal molecular nuances not observed with microscopy. Caution must be exercised in interpreting multimodal imaging results stipulated on a coincidental relationship between metabolic and morphometric borders of cancer, at least within animal models used in preclinical research. |
| Databáze: | OpenAIRE |
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