By blocking of an enzyme that affects the cellular microenvironment it is possible to stop brain tumour cells from growing. This is shown in a new study published in Molecular Cancer Therapeutics.
Brain tumours constitute 25% of all childhood cancers. Among those are malignant forms such as medulloblastoma, a cancer of the cerebellum. Today, more than half of the medulloblastoma patients can be cured, but there is a need for new treatments. The ability of the tumor cells to metastasize locally within the brain is a significant clinical problem, which causes the disease to recur even after the original tumor is surgically removed.
The present study focuses on proteoglycans, a group of molecules that are commonly found in the brain, and that consists of proteins with one or several attached carbohydrate chains. The enzyme that degrades these chains is called heparanase, and the researchers found that medulloblastoma cells, as well as cells from other childhood brain tumours, need this enzyme, which may suggest new ways to treat the tumor.
– Cancer cells invade the normal brain, which makes them difficult to treat. During this invasion, the tumor cells break down the proteoglycans that are found on and between the cells. When we blocked the enzyme heparanase, that degrades proteoglycans, it stopped the growth of the tumor cells, says Karin Forsberg Nilsson (Uppsala University/SciLifeLab), who has led the study.
The researchers found much higher levels of heparanase in childhood brain tumours than in the normal brain, and furthermore, a molecule that can block this enzyme induces cell death in medulloblastoma cells in culture, while normal brain cells were not affected. In mouse experiments, the researchers found that blocking heparanase shrank the tumours by 80%.
– The study increases our knowledge of how cancer cells interact with the tumor microenvironment. We hope that this can be of use for new therapies, says Argyris Spyrou, PhD student at the Department of Immunology, Genetics and Pathology, Uppsala University, first author of the study.
The study was performed in collaboration with researchers at Bruce Rappaport Faculty of Medicine, Haifa, Israel och Zucero Therapeutics, Brisbane, Queensland, Australia.