Chemokines are key
How chemokines exert their decisive role in inflammation and cancer was recently elucidated by a research team led by ISAR Chairman Martin Lohse.
An international team of researchers led by ISAR Chairman Martin Lohse used advanced microscopy technologies to investigate how a specific chemokine receptor (CXCR4) behaves on the cell surface. The team reports formation of receptor dimers, which appears to be particularly prominent on cancer cells that have a lot of these receptors. Compounds that block this dimerization might become future drugs.
Background: Chemokines are important messengers in inflammation, cell migration and cancer. They cause different cells to set out on their journey. In the development of an organism, they ensure that cells find their place. In inflammation, they attract immune cells to the site. And they also seem to play a role in the metastasis of cancer cells. They are interesting for stem cell researchers because with their help stem cells could be brought to where they are needed to regenerate diseased tissue.
Study details: There are many different chemokines and also many receptors that recognize them. Martin Lohse’s team has found out how such chemokine receptors interact. Together with researchers from the Netherlands, Great Britain and Belgium, the scientists investigated how a specific chemokine receptor, called CXCR4, behaves on the cell surface. In their publication in the renowned journal Proceedings of the National Academy of Sciences USA, they report that the more receptors there are on a cell, the more do the receptors form dimers. On cancer cells, which often carry very many of these receptors, dimer formation therefore predominates. Certain substances that block the CXCR4 receptors also inhibit pair formation. Such substances might be of particular use for future cancer therapies.
Işbilir A, Möller J, Arimont M, Bobkov V, Perpiñá-Viciano C, Hoffmann C, Inoue A, Heukers R, de Graaf C, Smit MJ, Annibale P, Lohse MJ (2020) Advanced fluorescence microscopy reveals disruption of dynamic CXCR4 dimerization by subpocket-specific inverse agonists. Proc Natl Acad Sci U S A 117: 29144-29154.