Despite extraordinary therapeutic advances, cancer is still the second most frequent cause of death within the EU, after cardiovascular diseases. Patient survival is heavily dependent on the type of cancer and whether or not the cancer has metastasized. What is metastasis? One can think of metastatic cancer cells as the ‘Christopher Columbus’ cells of the tumour. These cells are able to leave the site where they initially grow, spread (invade) throughout the tissue, and eventually colonize distal organs in the body causing the majority of deaths among cancer patients. One impediment to understanding metastasis has been the limited tools we have available to visualize cancer cell invasion in vivo, in real time, in a genetically tractable animal model.
To overcome these limitations, a major goal of the Huisken lab is to systematically study cancer cell invasion and metastasis in the zebrafish model by developing non-invasive biomedical imaging technologies. Did I say fish? Yes, zebrafish is an attractive laboratory animal to study cancer biology because it can be used to model nearly any known human tumour, with similar morphology and similar gene expression profiles. Zebrafish produce hundreds of embryos that are mostly translucent, enabling deep tissues to be readily imaged at subcellular resolution. How are fluorescently labelled cancer cells visualized in the zebrafish? One of the technologies that are being developed in the lab is Selective Plane Illumination Microscopy (SPIM). This is not your typical fluorescence microscopy technique; it uses a focused light-sheet to illuminate the specimen from the side, which provides excellent resolution at high penetration depths while being minimally invasive. Moreover, SPIM offers a number of advantages over established techniques such as reduction of photo-bleaching, high dynamic range, and high acquisition speed. Currently in the lab, we have built several custom-designed SPIM systems capable of long-term 4D time-lapse imaging, unprecedented spatio-temporal resolution and high-throughput, all critical to study cancer cell invasion and metastasis in vivo. We can now image cancer cell invasion in a physiologically relevant setting, which may well lead to crucial new insights into human disease.
Cancer is a complicated disease, in fact, it is “hundreds of diseases” all together. We reasoned that unconventional problems, such as cancer, require unconventional experiments to study them. There is great value in tackling the cancer problem using skills from different scientific disciplines. As a cancer cell biologist, I feel very privileged to be able to conduct this research in a multidisciplinary environment. The Huisken lab and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, are perfect examples of a multidisciplinary scientific exchange. MPI-CBG houses top-notch biologists, physicists, mathematicians, computational scientists, and world renown zebrafish, microscopy, and imaging-analysis core facilities, all critical for the advancement of our cancer studies. I believe our cancer zebrafish model, combined with novel microscopy technologies like SPIM, will reveal exciting new insights into the mechanism of metastasis in vivo and will hopefully contribute to the development of novel treatments for cancer patients.