#MBT2 TASK3 PC#

On the basis of those preliminary works, we explored here the predictive ability of the most abundant ether glycerophospholipids (GP) (i.e., plasmanyl phosphatidylcholine (PC-O), plasmenyl PC (PC-P), plasmanyl phosphatidylethanolamine (PE-O), and plasmenyl PE (PE-P) lipid species, Scheme 1), as biomarkers related to the physiological stages of tumor cells constituting the xenografts.Д®ther GP species differ from the more common diacyl subclass in having a fatty alcohol rather than a fatty acid at the sn-1 position. Some attempts to find such biomarkers by using IMS were carried out, but the results were limited to a single type of xenograft and may not hold for xenografts from different cell lines. ДЄn attractive approach to identify a valid biomarker that would correlate with the physiological stage of tumor cells may be to analyze the distribution of metabolites within xenograft samples by imaging mass spectrometry (IMS). That is, as it happens in clinical tumors, xenografts are formed by cells at different physiological stages, exposed to slightly different environments depending on their distance to the blood vessels, hindering altogether the comparison between samples. For example, a rapid growth may lead to a poor vascularization of the tissue, which in turn may result in a generalized hypoxic state and, eventually, in cell death. However, within a same experiment, xenografts usually differ in their morphology, growth rate, and vascularization level. One of the main advantages of this model is the possibility of evaluating the response to the treatment in human-originated cells and in a more physiological context than a culture dish. They are commonly developed in immunocompromised (nude) mice by injecting human tumor cells subcutaneously or onto a specific tissue in which the tumor originated. Xenografts are a useful model to evaluate the pathobiology of tumors and to investigate the response to new antitumor drug candidates for human treatment. 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. 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. 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. 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.

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. 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. However, because of their heterogeneity, analysis of the results is often controversial.

Xenografts are commonly used to test the effect of new drugs on human cancer.

Mbt2 task3