Glioblastoma multiforme influence on the elemental homeostasis of the distant organs: the results of inter-comparison study carried out with TXRF method

Abstract

Glioblastoma (GBM) is a fast-growing and aggressive brain tumor which invades the nearby brain tissue but generally does not spread to the distant organs. Nonetheless, if untreated, GBM can result in patient death in time even less than few months from the diagnosis. The influence of the tumor progress on organs other than brain is obvious but still not well described. Therefore, we examined the elemental abnormalities appearing in selected body organs (kidney, heart, spleen, lung) in two rat models of GBM. The animals used for the study were subjected to the implantation of human GBM cell lines (U87MG and T98G) characterized by different levels of invasiveness. The elemental analysis of digested organ samples was carried out using the total reflection X-ray fluorescence (TXRF) method, independently, in three European laboratories utilizing various commercially available TXRF spectrometers. The comparison of the data obtained for animals subjected to T98G and U87MG cells implantation showed a number of elemental anomalies in the examined organs. What is more, the abnormalities were found for rats even if neoplastic tumor did not develop in their brains. The most of alterations for both experimental groups were noted in the spleen and lungs, with the direction of the found element changes in these organs being the opposite. The observed disorders of element homeostasis may result from many processes occurring in the animal body as a result of implantation of cancer cells or the development of GBM, including inflammation, anemia of chronic disease or changes in iron metabolism. Tumor induced changes in organ elemental composition detected in cooperating laboratories were usually in a good agreement. In case of elements with higher atomic numbers (Fe, Cu, Zn and Se), 88% of the results were classified as fully compliant. Some discrepancies between the laboratories were found for lighter elements (P, S, K and Ca). However, also in this case, the obtained results fulfilled the requirements of full (the results from three laboratories were in agreement) or partial agreement (the results from two laboratories were in agreement).

Figure 1

Box-and-whiskers plots presenting the ranges of P and S concentrations in kidneys, hearts, spleens and lungs taken from animals representing N (green), T (blue) and U (violet) groups obtained through the cooperating laboratories (from left to right: L1, L2 and L3). Median, interquartile range and minimal-maximal values are marked as a small square, a box and whiskers, respectively. The statistically significant differences (p-value < 0.05), comparing to control group, are signed with stars.

Figure 2

Box-and-whiskers plots presenting the ranges of K and Ca concentrations in kidneys, hearts, spleens and lungs taken from animals representing N (green), T (blue) and U (violet) groups obtained through the cooperating laboratories (from left to right: L1, L2 and L3). Median, interquartile range and minimal-maximal values are marked as a small square, a box and whiskers, respectively. The statistically significant differences (p-value < 0.05), comparing to control group, are signed with stars.

Figure 3

Box-and-whiskers plots presenting the ranges of Fe concentration in kidneys, hearts, lungs and spleens taken from animals representing N (green), T (blue) and U (violet) groups obtained through the cooperating laboratories. Median, interquartile range and minimal-maximal values are marked as a small square, a box and whiskers, respectively. The statistically significant differences (p-value < 0.05), comparing to control group, are signed with stars. For better visualization the data obtained for spleen were presented separately.

Figure 4

Box-and-whiskers plots presenting the ranges of Cu concentration in kidneys, hearts, lungs and spleens taken from animals representing N (green), T (blue) and U (violet) groups obtained through the cooperating laboratories. Median, interquartile range and minimal-maximal values are marked as a small square, a box and whiskers, respectively. The statistically significant differences (p-value < 0.05), comparing to control group, are signed with stars. For better visualization the data obtained for kidneys were presented separately.

Figure 5

Box-and-whiskers plots presenting the ranges of Zn and Se concentrations in kidneys, hearts, spleens and lungs taken from animals representing N (green), T (blue) and U (violet) groups obtained through the cooperating laboratories (from left to right: L1, L2 and L3). Median, interquartile range and minimal-maximal values are marked as a small square, a box and whiskers, respectively. The statistically significant differences (p-value < 0.05), comparing to control group, are signed with stars.