World Cancer Day takes place annually on 4 February. Its aim is to raise public awareness of the prevention, research and treatment of cancer. Reason enough to present a particularly innovative research project for the treatment of pancreatic cancer. For the first time, a team from the Department of Life Sciences at IMC University of Applied Sciences Krems is researching on a novel optogenetic tumour cell line. It is a promising tool to better understand the underlying molecular mechanisms and thus also to find strategies for new therapeutic approaches.
Optogenetics for receptor control
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide and one of the greatest challenges in oncology due to late diagnosis and lack of complete recovery of health. A team of researchers from the Department of Life Sciences has therefore set itself the goal to develop novel cell culture models to study the underlying molecular mechanisms in pancreatic cancer and to identify potential therapeutics. The researchers are using the novel method of optogenetics for this purpose. Research results have already been published in international journals and speak for the success of the new method.
Optogenetics is probably one of the most innovative methods to be found in the toolbox of science. The mix of optical technologies and genetics allows researchers, for example, to control the activity of targeted receptors in human cells with extreme precision. More precisely, light-sensitive protein domains (specific parts of a protein) are isolated from plants and incorporated into the receptors to be studied. In this way, they can be switched on or off by light stimuli. We find a comparable principle in the plant world: here, too, plants react to light and only grow when they are exposed to sunlight.
In the current research project, the researchers have specialised in the so-called Toll-like Receptor 4 (TLR4), which is expressed at a significantly higher level in 70% of pancreatic cancer patients and is thus to a considerable extent responsible for the development and progression as well as the aggressiveness of this form of cancer. In order to better investigate the receptor, it was fused with the so-called light-oxygen-voltage (LOV) protein domain, which was isolated from the genus of yellow-green algae. The receptor, which can now be induced by light, was then integrated into the genome of the tumour cell via viruses and can thus be switched on by exposure to blue light or switched off again in the dark.
Advantages over conventional methods
This cell culture model can thus contribute significantly to the investigation of genes/proteins that play a central role in the development and progression of pancreatic cancer (basic research) and to the identification of novel therapeutics (preclinical studies). The possibility of activating TLR4 by exposing it to blue light or deactivating it in the dark brings some advantages over current test systems based on the application of agonists or antagonists. For example, it is possible to achieve spatial as well as temporal control of the receptor, which is only possible to a limited extent through treatment with stimulators and inhibitors in conventional test systems. Furthermore, a precise activation or inactivation can be ensured, since the activation by means of light very specifically affects only the optogenetic receptor. In contrast, the application of agonists and antagonists often acts on several receptors and thus leads to the activation or inactivation of several signalling pathways. A clear advantage was also discovered with regard to the application of 3-D cell culture models, which are increasingly playing a greater role in preclinical studies because they better mimic the human environment. Light has the ability to penetrate even into the innermost layer of a spheroid (microtumour), while substances diffuse much more weakly. In addition, the use of light over substances represents a more consistent and easier application, as potential errors in the production and administration of the substances can be avoided and are associated with low costs.
