High-grade
gliomas (
glioblastomas) are the most common and deadly
brain tumors in adults, currently with no satisfactory treatment available. Apart from de novo
glioblastoma, it is currently accepted that these
malignancies mainly progress from lower grade glial
tumors. However, the molecular entities governing the progression of
gliomas are poorly understood. Extracellular and
membrane proteins are key biomolecules found at the cell-to-cell communication interface and hence are a promising
proteome subpopulation that could help understand the development of
glioma. Accordingly, the current study aims at identifying new
protein markers of human
glioma progression. For this purpose, we used glial
tumors generated orthotopically with T98G and U373 human
glioma cells in nude mice. This setup allowed also to discriminate the
protein origin, namely, human (
tumor) or mouse (host). Extracellular and
membrane proteins were selectively purified using biotinylation followed by
streptavidin affinity chromatography. Isolated
proteins were digested and then identified and quantified employing 2D-nano-HPLC-MS/MS analysis. A total of 23 and 27 up-regulated extracellular and
membrane proteins were identified in the T98G and U373 models, respectively. Approximately two-thirds of these were predominantly produced by the
tumor, whereas the remaining
proteins appeared to be mainly overexpressed by the host tissue. Following extensive validation, we have focused our attention on sparc-like
protein 1. This
protein was further investigated using immunohistochemistry in a large collection of human
glioma samples of different grades. The results showed that sparc-like
protein 1 expression correlates with
glioma grade, suggesting the possible role for this
protein in the progression of this
malignancy.