New therapeutic principles and biological mechanisms related to brain tumour cell invasion and angiogenesis

Primary gliomas represent one of the greatest challenges in neuro-oncology. Recent studies have identified so-called ?cancer stem cells? in several cancers. These cells have the capacity to proliferate and establish tumors in laboratory animals after inje ction of only a small number of cells. Moreover, cancer stem cells are resistant to radiation- and chemotherapy, which may explain why many tumors regress significantly with current treatment regimens, only to recur later with more malignant properties. A major research question in our laboratory is to identify the nature and origin of the cancer stem cell. Do cancer stem cells originate from more differentiated cells that become mutated and acquire stem cell-like properties? Or, do they originate from th e normal neural stem cell population present in the brain that has undergone oncogenic transformation? Here we propose to characterize the cancer stem cell in glioblastoma and explore whether and how such a normal-to-cancer stem cell conversion occurs..A second major research theme is to identify the key molecular events that drive invasive and angiogenic properties of cancer and cancer stem cells. This includes studies on the mechanisms required to establish an invasive or angiogenic phenotype. Using adv anced animal models, we will compare the protein expression profiles of a highly invasive, non-angiogenic stem cell like tumour to less invasive, highly angiogenic tumor phenotypes. The overall aim of our research is to identify basic processes involved i n tumour formation and characterize key molecules involved in invasion and angiogenesis. This will allow the development of more effective and targeted brain tumour therapies.