title: Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry.
abstract: Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na(+) adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na(+)/K(+) ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na(+) and K(+) adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results. Graphical Abstract ᅟ.
authors.affiliation: Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Bilbao, 48940, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernández
authors.affiliation: Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Bilbao, 48940, Spain.
authors.forename: Jone
authors.initials: J
authors.lastname: Garate
authors.affiliation: Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Bilbao, 48940, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lage
authors.affiliation: Unité de recherche Inserm 0916, Institut européen de chimie et biologie (IECB)-INSERM, 2, rue Robert Escarpit, 33607, Pessac, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Terés
authors.affiliation: Laboratory of Molecular and Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122, Palma, Balearic Islands, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Higuera
authors.affiliation: Research Unit, Hospital Universitari Son Espases, Institut d'Investigació Sanitària de Palma (IdISPa), Ctra. Valldemossa 79, E-07010, Palma, Balearic Islands, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bestard-Escalas
authors.affiliation: Research Unit, Hospital Universitari Son Espases, Institut d'Investigació Sanitària de Palma (IdISPa), Ctra. Valldemossa 79, E-07010, Palma, Balearic Islands, Spain.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: López
authors.affiliation: Laboratory of Molecular and Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122, Palma, Balearic Islands, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Guardiola-Serrano
authors.affiliation: Laboratory of Molecular and Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122, Palma, Balearic Islands, Spain.
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Escribá
authors.affiliation: Research Unit, Hospital Universitari Son Espases, Institut d'Investigació Sanitària de Palma (IdISPa), Ctra. Valldemossa 79, E-07010, Palma, Balearic Islands, Spain. gwendolyn.barcelo@ssib.es.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Barceló-Coblijn
authors.affiliation: Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Bilbao, 48940, Spain. josea.fernandez@ehu.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D064593:Heterografts; D006801:Humans; D008055:Lipids / Q000032:analysis* / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008819:Mice, Nude; D009336:Necrosis / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000032:analysis / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000032:analysis / Q000378:metabolism; D010955:Plasmalogens / Q000032:analysis; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D012964:Sodium / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D008055:Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010955:Plasmalogens; C483858:phosphatidylethanolamine; D012964:Sodium; D011188:Potassium
keywords: Biomarkers; Ether lipids; Imaging mass spectrometry; Lipidomics; Xenografts