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Biology: Publication in Nature Communications
Metastases, i.e. the secondary growths of cancer cells, are a key problem in many types of cancer. As descendants of the primary tumour, they can grow in other organs distant from the primary site and are often difficult to identify. A research team from the Institute of Genetics at Heinrich Heine University Düsseldorf (HHU) has now identified molecular mechanisms, which can enable cancer cells to colonise other tissue. The team led by Dr Tobias Reiff has now published its findings in the scientific journal Nature Communications.
Tumours develop when cells undergo such mutation that important functions are lost. These cells can then often divide indefinitely as the cell death mechanism is disabled or they are capable of bypassing the immune system. In most cases, if a tumour is discovered in good time, it can be treated: by means of operations, radiotherapy or chemotherapy – often in combination. Depending on the organ and type of tumour, the chances of recovery are often good.
The research group led by Dr Reiff is concentrating on colorectal tumours, which are often only discovered at a late stage. Reiff explains: “By that time, the cancer may have already spread, making it more dangerous: Individual cancer cells can infiltrate and colonise other tissue, where they grow and then destroy other vital organs.” According to the German Cancer Research Centre (DKFZ), around 90% of cancer patients die as a result of metastases rather than the primary tumour (https://www.krebsinformationsdienst.de/aktuelles/detail/metastasen-die-toedliche...; German only).
Reiff and his team are examining how cells separate from the primary tumour, spread via the bloodstream or lymphatic system (referred to as “dissemination”) and then colonise other tissue (“homing”). “These processes are not well understood. Contrary to formerly accepted wisdom, we now know that tumours can already spread at an early stage. Initially, however, the body’s own defence mechanisms can still prevent the spread of these disseminated cells successfully in most cases,” says Reiff.
The researchers have now identified signalling molecules called Netrins and the corresponding receptor (“Frazzled/Deleted in Colorectal Cancer”, for short: DCC), which control when the individual cells separate from the tumour and migrate. The fruit fly Drosophila melanogaster served as the research subject. It is particularly well suited as a model organism, as the flies have short lifecycles and reproduce on a daily basis.
“If we can gain an understanding of the underlying metastasis mechanisms in Drosophila, we may also be able to identify starting points for human therapies,” says Dr Lisa Zipper, lead author of the study in Nature Communications. There are great similarities at genetic level, e.g. large sections of the tumour-driving signalling pathways – which determine the frequency of division, cell death and cell fate – are the same.
The researchers in Düsseldorf are examining the flies using advanced laser microscopy techniques. Using proteins with fluorescent markings – which can be made visible on a selective basis via laser impulses – they traced how stem cells migrate and which molecules may be involved in metastasis. The researchers have named the new experimental approach developed for this work “Hamelin Assay” after the legend of the Pied Piper of Hamelin. It has enabled them to determine in detail how the migrating cells are guided through the intestine by the Netrins – like the rats in the legend are lured by the music from the rat-catcher’s pipe.
“This receptor molecule is altered in around 65% of colorectal cancer patients, which is a good indicator that the Netrins play a role in the spread of cancer,” says Reiff. Further studies are now needed to show whether the DCC receptor can be a starting point for future therapies aimed at countering metastasis.
The research work was funded by the Wilhelm Sander Foundation and the German cancer research/support organisation, Deutsche Krebshilfe.
Detailed caption:
The newly developed Hamelin Assay shows how Netrin molecules (white dots) induce the migration of cancer cells through organ boundaries (red line) via the Fra/DCC receptors in intestinal stem cells (green cells). The rat-catcher blowing the Netrins out of his pipe symbolises how the disseminated cancer cells move through the body to form subsequent metastases. (Image: HHU/Tobias Reiff)
Lisa Zipper, Pol Ramon-Cañellas, Filiz Akkas-Gazzoni & Tobias Reiff; Frazzled/DCC directs spatial progenitor integration ensuring steady-state intestinal turnover; Nature Communications 17, 2491 (2026)
DOI: 10.1038/s41467-026-70704-9
The newly developed Hamelin Assay. A detailed caption can be found at the end of the article.
Copyright: HHU/Tobias Reiff
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The newly developed Hamelin Assay. A detailed caption can be found at the end of the article.
Copyright: HHU/Tobias Reiff
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