Abstract
PurposeGlioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults. In the present study, we investigate the role of the complement system in the glioblastoma situation in an experimental model, since we have previously been able to show a blockade of this system in the glioblastoma setting.Technique and resultsA GFP-positive glioblastoma cell line was used to induce glioblastomas subcutaneously in rats (n=42). Antibodies against C1-Inactivator (C1-IA) were used to try to re-activate the complement system. We were able to demonstrate an increased survival in rats treated with anti-C1-IA with an intratumoral route, and we could establish the same the results in a second series. Serum analyses revealed decreased levels of IL-1b and GM-CSF in animals 24 days after tumor cell inoculation in the anti-C1-IA group when compared to controls. Immunohistochemistry revealed decreased expression of C1-IA following treatment.InterpretationThese results are in line with our previous work showing an upregulation of C1-IA, which is able to block the classical complement pathway, in glioblastomas. Treatment with antibodies against C1-IA seems to be beneficial in the glioblastoma situation, and no side effects could be seen in our experiments.
Highlights
Glioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults
In 2005 Temozolomide was approved by the Food and Drug Administration (FDA) for treating GBM and subsequently Avastin (Bevacizumab) has been approved
We have recently described that C1-IA, denoted C1-inhibitor (C1-inh, C1 esterase inhibitor, serpin family G member 1), is overexpressed in glioblastomas on the gene level, protein level, and on glioblastoma cells from patients as well as and in rat glioma cell lines [3], which introduces inactivation of the complement system as an important factor to be considered in glioblastoma research
Summary
Glioblastoma multiforme (GBM) or astrocytoma grade IV is the most common type of primary brain tumor in adults. It has a capacity to spread and infiltrate normal surrounding brain tissue which limits the multimodality treatment currently used comprising neurosurgery, chemotherapy and radiotherapy, and makes complete resection virtually impossible [1]. In 2005 Temozolomide was approved by the Food and Drug Administration (FDA) for treating GBM and subsequently Avastin (Bevacizumab) has been approved. We have recently described that C1-IA (complement1-inactivator), denoted C1-inhibitor (C1-inh, C1 esterase inhibitor, serpin family G member 1), is overexpressed in glioblastomas on the gene level, protein level, and on glioblastoma cells from patients as well as and in rat glioma cell lines [3], which introduces inactivation of the complement system as an important factor to be considered in glioblastoma research. The complement system comprises three biochemical pathways; the classical, the alternative, and the lectin induced pathways, and under normal conditions the complement system acts as a functional bridge between the innate and the adaptive immune responses [4]
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