Article
Tumor-host interactions in an animal model revealed by quantitative mass spectroscopy
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Published: | May 20, 2009 |
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Objective: A human xenograft model of human glioblastoma (GBM) has been developed by the implantation of human GBM spheroids into the brains of nude rats. We have recently shown that the tumours that develop show a highly infiltrative, diffuse, non-angiogenic phenotype (first generation tumours). This phenotype is characterized by an up-regulation of stem cell markers. By serial transplantation in animals, a phenotypic shift occurs that leads to a more angiogenic phenotype. This is accompanied by a loss of stem cell markers. The objective of the presented work was to use a proteomics approach to identify putative markers associated with the infiltrative phenotype.
Methods: We used high throughput protein profiling technology based on isobaric peptide labelling and quantitative mass spectrometry on MALDI TOF/TOF on membrane-enriched fractions of the tumor phenotypes.
Results: We identified 850 non redundant proteins in 'lighter' and 918 proteins (CI 95%) in the 'heavier' membrane fractions respectively. Of these, 413 and 375 were quantifiable. Preliminary analyses indicate that many of the proteins identified are involved in tumor angiogenesis, invasion and progression. One of the differentially expressed proteins (alpha-basic crystallin) is currently validated in clinical samples.
Conclusions: We have developed a highly infiltrative animal model for human GBM and identified high throughput proteomics, a number of markers on the cell surface of the infiltrative tumour cells used. Such markers may represent novel molecular targets for therapy.