Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry
Roberto Fernández1, Jone Garate1, Sergio Lage1
1Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Bilbao, 48940, Spain.
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.
Insights
Imaging mass spectrometry analyzes xenograft tumor composition. Necrotic areas show higher phosphatidylcholine (PC) ether derivatives, while phosphatidylethanolamine (PE) ether derivatives indicate viable tissue.
Area of Science:
- Biomedical research
- Analytical chemistry
- Cancer biology
Background:
- Xenografts are crucial for cancer drug testing but suffer from heterogeneity.
- Tumor cell metabolic diversity (metastatic to necrotic) complicates result interpretation.
- Imaging mass spectrometry (IMS) offers detailed tissue composition and biomolecule distribution analysis.
Purpose of the Study:
- To investigate the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their ether derivatives in diverse human cancer xenografts.
- To assess the utility of IMS in differentiating tumor regions based on lipid profiles.
- To correlate specific lipid species and adducts with tumor viability and necrosis.
Main Methods:
- Utilized imaging mass spectrometry (IMS) to analyze xenografts from five human cancer cell lines (A-549, NCI-H1975, BX-PC3, HT29, U-87 MG).
- Quantified the spatial distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O, PE-P/O).
- Analyzed the abundance of sodium (Na+) and potassium (K+) adducts in relation to lipid species and tissue regions.
Main Results:
- Necrotic areas exhibited higher abundance of Na+ adducts and PC-P/O species.
- PE-P/O species were found abundantly across all analyzed xenografts.
- Distinct ratios of PC/PC-ether and Na+/K+ were observed, potentially marking necrotic regions.
- Increased PE-ether species suggested the presence of viable tumor tissues.
Conclusions:
- IMS can effectively map lipid distributions within xenografts, aiding in the interpretation of heterogeneous tumor environments.
- Specific lipid ether derivatives (PC-P/O, PE-P/O) and ion adducts (Na+, K+) serve as potential biomarkers for distinguishing necrotic from viable tumor tissues.
- Careful consideration of Na+ and K+ adduct variations is essential for accurate IMS data interpretation in xenograft studies.
