Effects of class-3 semaphorins on brain tumour progression

Malignant brain tumors belong to the most frequent tumor encountered in childhood. Standard treatment modalities are neurosurgical resection, chemotherapy and irradiation. In contrast to the excellent results of well established treatment studies in pediatric patients suffering from leukaemia cure rates of children with malignant brain tumors remained low. Therefore the development of new antitumor strategies has become a major assignment in experimental neurology. Class-3 semaphorins have been first identified as axon guidance factors and during the last years it was found that some are able to inhibit angiogenesis and as a result they are candidates for the inhibition of tumor development. Goal of the project was to determine if class-3 semaphorins can be used for the treatment of brain cancer. For this reason U87MG glioma cells were lentivirally transfected with class-3 semaphorins and implanted in the brain cortex of mice. The expression of Semaphorin3D completely inhibits the development of tumors from these cells. The tumor inhibition was correlated with a dramatic effect on the survival of mice, as in the groups after the implantation of semaphorin expressing cells was a very substantial decrease in survival. Additionally the expression of recombinant semaphorin3D changes the migration and cell adhesion of U87MG cells in comparison to control cells. The goal for the near future is the treatment of growing brain tumors in a mouse model with recombinant semaphorins with the help of osmotic pumps.