Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets.

Trace Element Concentration Changes in Brain Tumors: A Review

“…Chandra et al () investigated magnesium concentration in primary tumor cells and infiltrating tumor cells in rat brains, and both these tumor cells indicated a significantly higher magnesium concentration compared to adjacent healthy brain tissue. Magnesium was also measured by Andrási et al () in brains with and without tumors; however, the results were not significant, and trends were not mentioned.…”

“…Magnesium is important for the normal functioning of cells, as well as for proliferation of cells. Therefore, alterations of magnesium homeostasis can lead to abnormal cell growth (Chandra et al, ). Since tumor cells have an accelerated growth rate, a high magnesium content is to be expected.…”

“…Thus, apart from comparing relative differences, actual concentration levels between tumor types from different studies could not be done. Furthermore, three of the 11 studies were conducted on tumors in rats (Takeda et al, ; Takeda et al, ; Chandra et al, ). Although these concentrations levels cannot be compared to brain tumors occurring in humans, the rat studies can confirm a change trend for element levels.…”

“…Trace elements have been implicated in the progression of cancer, since the concentration differs between cancerous and noncancerous tissue, different cancer types, and different malignancy grades (Mulware, ; Chandra et al, ). Several studies have focused on trace element levels in cancerous and noncancerous tissue from different organs, breast cancer being one of the most studied (Zhuang et al, ; Mulware, ).…”

Pathological Brain Detection by Artificial Intelligence in Magnetic Resonance Imaging Scanning (Invited Review)

“…Neoplastic disease: First is neoplastic disease (also called tumor). The primary neoplastic disease starts in brain and remains therein [20], while the secondary starts elsewhere and then travels to the brain [21]. Benign tumors do not have cancer cells, rarely spread, and may cause problems if pressing certain brain areas.…”