Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models

No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling al...

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Main Authors: Xin Ma, Andro Botros, Sylvia R. Yun, Eun Young Park, Olga Kim, Soojin Park, Thu-Huyen Pham, Ruihong Chen, Murugesan Palaniappan, Martin M. Matzuk, Jaeyeon Kim, Facundo M. Fernández
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Chemistry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2023.1332816/full
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author Xin Ma
Andro Botros
Sylvia R. Yun
Eun Young Park
Olga Kim
Soojin Park
Thu-Huyen Pham
Ruihong Chen
Murugesan Palaniappan
Murugesan Palaniappan
Martin M. Matzuk
Martin M. Matzuk
Jaeyeon Kim
Facundo M. Fernández
Facundo M. Fernández
author_facet Xin Ma
Andro Botros
Sylvia R. Yun
Eun Young Park
Olga Kim
Soojin Park
Thu-Huyen Pham
Ruihong Chen
Murugesan Palaniappan
Murugesan Palaniappan
Martin M. Matzuk
Martin M. Matzuk
Jaeyeon Kim
Facundo M. Fernández
Facundo M. Fernández
author_sort Xin Ma
collection DOAJ
description No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n = 4) of high-grade serous ovarian cancer (HGSOC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes were compared to those in healthy mouse reproductive tissue (n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.
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spelling doaj.art-4136372308ec4b55ab4eeaf71e2b8aa32024-01-08T04:24:56ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462024-01-011110.3389/fchem.2023.13328161332816Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse modelsXin Ma0Andro Botros1Sylvia R. Yun2Eun Young Park3Olga Kim4Soojin Park5Thu-Huyen Pham6Ruihong Chen7Murugesan Palaniappan8Murugesan Palaniappan9Martin M. Matzuk10Martin M. Matzuk11Jaeyeon Kim12Facundo M. Fernández13Facundo M. Fernández14School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesCenter for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesCenter for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartments of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United StatesSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, United StatesPetit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United StatesNo effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout (n = 4) and triple mutant mouse models (n = 4) of high-grade serous ovarian cancer (HGSOC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes were compared to those in healthy mouse reproductive tissue (n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.https://www.frontiersin.org/articles/10.3389/fchem.2023.1332816/fullmass spectrometry imagingmatrix-assisted laser desorption/ionizationhigh-grade serous ovarian cancerlipidomicsbiomarkers mass spectrometry imagingbiomarkers
spellingShingle Xin Ma
Andro Botros
Sylvia R. Yun
Eun Young Park
Olga Kim
Soojin Park
Thu-Huyen Pham
Ruihong Chen
Murugesan Palaniappan
Murugesan Palaniappan
Martin M. Matzuk
Martin M. Matzuk
Jaeyeon Kim
Facundo M. Fernández
Facundo M. Fernández
Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
Frontiers in Chemistry
mass spectrometry imaging
matrix-assisted laser desorption/ionization
high-grade serous ovarian cancer
lipidomics
biomarkers mass spectrometry imaging
biomarkers
title Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
title_full Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
title_fullStr Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
title_full_unstemmed Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
title_short Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models
title_sort ultrahigh resolution lipid mass spectrometry imaging of high grade serous ovarian cancer mouse models
topic mass spectrometry imaging
matrix-assisted laser desorption/ionization
high-grade serous ovarian cancer
lipidomics
biomarkers mass spectrometry imaging
biomarkers
url https://www.frontiersin.org/articles/10.3389/fchem.2023.1332816/full
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