Blocked enzyme can stop growth in brain tumour cells
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 the journal Molecular Cancer Therapeutics by researchers at Uppsala University in collaboration with researchers in Haifa, Israel and Brisbane, Australia.
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 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, professor at the Department of Immunology, Genetics and Pathology, Uppsala University and 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 is collaboration between researchers at Uppsala University, Bruce Rappaport Faculty of Medicine, Haifa, Israel och Zucero Therapeutics, Brisbane, Queensland, Australia
Spyrou et al. (2017) Inhibition of Heparanase in Pediatric Brain Tumor Cells Attenuates their Proliferation, Invasive Capacity, and In Vivo Tumor Growth. Molecular Cancer Therapeutics, http://mct.aacrjournals.org/content/early/2017/07/17/1535-7163.MCT-16-0900
Science for Life Laboratory (SciLifeLab) is a Swedish national centre for molecular biosciences with the focus on health and environmental research. The centre combines advanced technical know-how and state-of-the art equipment with a broad knowledge of translational medicine and molecular bioscience.