Oxygen-deprived tumors are often more aggressive. Tumor cells grow faster than new blood vessels can be formed and the existing blood vessels within the tumor are often weak and unable to supply oxygen efficiently. Despite the intensive efforts to treat the most aggressive variant, glioblastoma, the tumor inevitably returns. Now researchers at Lund University have discovered that only a small proportion of the cells in the tumor – cancer stem cells – are resistant to treatment. In a study conducted partly on mice and partly on human glioma cells, the research team has discovered that a specific marker (CD44) present on the surface of the cancer stem cells interacts with a protein (HIF-2a) which is central to the adaptation to oxygen deprivation. When a normal cell becomes deprived of oxygen, HIF is stabilized by adaptations that save energy and help form new blood vessels. But in cancer stem cells, this signal pathway appears to be active even when the cells are not being deprived of oxygen. The study results indicate that the interaction with CD44 – which is specific to cancer stem cells – is crucial to this oxygen-independent stabilization of HIF. The findings explain how cancer stem cells can exploit HIF despite often being located in the parts of the brain tumor with the best oxygen supply, even next to blood vessels. Researchers believe these cancer stem cells could be responsible for recurrence of the disease and are pursuing further research.