Protein expression in experimental malignant glioma varies over time and is altered by radiotherapy treatment

Abstract

Radiotherapy is one of the mainstays of glioblastoma (GBM) treatment. This study aims to investigate and characterise differences in protein expression patterns in brain tumour tissue following radiotherapy, in order to gain a more detailed understanding of the biological effects. Rat BT4C glioma cells were implanted into the brain of two groups of 12 BDIX-rats. One group received radiotherapy (12 Gy single fraction). Protein expression in normal and tumour brain tissue, collected at four different time points after irradiation, were analysed using surface enhanced laser desorption/ionisation -time of flight -mass spectrometry (SELDI-TOF-MS). Mass spectrometric data were analysed by principal component analysis (PCA) and partial least squares (PLS). Using these multivariate projection methods we detected differences between tumours and normal tissue, radiation treatment-induced changes and temporal effects. 77 peaks whose intensity significantly changed after radiotherapy were discovered. The prompt changes in the protein expression following irradiation might help elucidate biological events induced by radiation. The combination of SELDI-TOF-MS with PCA and PLS seems to be well suited for studying these changes. In a further perspective these findings may prove to be useful in the development of new GBM treatment approaches.

Vandetanib alters the protein pattern in malignant glioma and normal brain in the BT4C rat glioma model

“…This is in concordance with previous findings in the same animal model (26). In the present study, the analysis has been expanded as compared to the previously published study, to include separate, thorough investigations of different durations of treatment in both tumor and contralateral normal tissue.…”

“…In many previous proteomic studies of glioma in vitro the analyses of protein expression have been done at a single time-point after treatment (22,23,42,44). Based on our findings, together with the information from the earlier referred study (26), we believe that the issue of proteomic response in malignant glioma to treatment is complex and that potential markers may be expressed differently in relation to timing of treatment and sampling of specimens.…”

“…The capacity of this method to analyze samples from cancer patients has been established previously (39,40). It has also been utilized to detect treatment-induced changes in the urinary proteome of patients with polycystic kidney diseases (41) as well as by our group for studying effects of radiotherapy in rat glioma (26). However, most previous studies on treatment-induced changes in glioma protein expression patterns have been performed in vitro (22,23,42).…”

“…To facilitate evaluation of analytical reproducibility a number of quality control (QC) samples were analyzed together with the other samples, randomly located to different spots on the ProteinChip arrays. The array preparation strategy has been described in detail elsewhere (26), below follows a short description.…”

Glioma-specific antigens for immune tumor therapy

“…Different methods of mass spectrometry have proven to be efficient for analyzing protein profiles in tumors and may be useful in the discovery of new attractive vaccine targets. The advantage of this system is that a large part of the proteome can be analyzed, providing information on upregulated proteins that can be targeted and is an important tool for prognosis of tumor progression [91][92][93].…”