A research group at the Department of Biochemistry and Molecular Biology of the University of Seville has made a significant advance by discovering the crucial role of the protein Galectin-3 in the progression of various types of brain tumours. In these tumours, the most abundant immune system cells, microglia and macrophages, overexpress Galectin-3, which creates an immunosuppressed environment which inhibits the action of other immune cells against cancer cells.
In vitro findings have shown that specific inhibition of Galectin-3 in microglial cells promotes expression of proinflammatory markers and reverses the presence of key immunosuppressive biomarkers. In vivo models of brain metastases of breast cancer and glioblastoma, two of the most common and aggressive types of brain tumours in the population, have validated these results. In genetically-modified models where Galectin-3 was knocked out, microglia cells and macrophages displayed a more inflammatory and anti-tumour state, leading to a reduction in the size of primary tumours and brain metastases by up to fivefold.
These results, although preclinical, have clear translational potential. Thanks to collaborations with Lund University, the research group has access to the TD006 antibody, a selective inhibitor of Galectin-3 currently being tested in clinical trials in Alzheimer’s patients. The team is currently working to improve Galectin-3 inhibitors so that they can improve their efficiency in reaching brain tumours, as well as researching their use in combination with other conventional therapies such as radiotherapy and chemotherapy.
Cancer Letters
Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth
16-Apr-2024