gms | German Medical Science

Objective: Human gliomas are not curable by surgical resection or adjuvant treatment. Nevertheless, any operation aims to improve the patient’s outcome by a reduction of the tumor volume. Tissue glues contain the serin protease thrombin (=coagulation factor II) as one of their main components. Our study shows that gliomas are significantly influenced by the thrombin-receptor-system that acts as a highly potent growth factor system. One dangerous result of this is that tissue glues and dural sealants massively increase the proliferation of human glioma cells, change their morphology and increase their motility.

Methods: Three intraoperatively used tissue glues and dural sealants, which contain thrombin as their main sticky component, were tested for their potential to influence glioma cell morphology, proliferation and invasion. In addition to that, five coagulation blocking preparations (antithrombin III, heparin, the low-molecular weight heparin preparations enoxaparin and nadroparin as well as hirudin of the leech) were tested for their effects on glioma cell biology.

Results: All tissue glue preparations and the dural sealant, which contain thrombin as their main sticky component significantly increase the glioma cell proliferation up to more than 200% of the basal level. The coagulation-inhibiting preparations antithrombin III, heparin, enoxaparin, nadroparin and hirudin significantly suppress glioma cell growth down to 30%. Analog results were obtained when glioma cell motility was tested with the modified Boyden chamber. Analog results were also seen in organotypic brain slices that showed an increased glioma cell motility and invasion in the presence of thrombin and a reduction of migration by use of the coagulation blockers.

This is confirmed by a change of the cellular morphology towards a more branched phenotype with cellular features of migrating cells, when thrombin containing preparations were used.

Conclusions: Intraoperatively used tissue glues and dural sealants, which contain thrombin as their main sticky component, massively increase human glioma cell aggressiveness. Our data predict a pro-proliferative effect of these preparations for invasive glioma cells. These stay inside the patient’s brain and are accessible via cerebrospinal fluid. This could disturb the primary aim of tumor-reductive surgery. Therefore, the use of tissue glues and dural sealants should be carefully considered in neurosurgical tumor treatment.