Swiss discovery may soon prevent tumour metastasis
Cancer metastases – spread through the body’s lymphatic system – account for nearly 90% of deaths in cancer patients. This has guided researchers from the Paul Scherrer Institute (PSI) in Switzerland, along with pharmaceutical company F. Hoffmann-La Roche (Roche), to develop an artificial agent against the metastasis of certain cancers, such as colorectal cancer.
In the body, about 20 chemokine receptor 7 proteins (CCR7) control the movement of cells within transport vessels and can interact with more than 40 signaling proteins called chemokines to elicit transport – as soon as the appropriate signaling protein outside the cell binds to it, a chain reaction in the cell causes the cell to move in the direction of the highest concentration of the signaling protein.Cancer cells can use this mechanism to spread in the body and eventually form metastases in other tissues.
To suppress the cancer metastasis process, researchers used X-ray crystallography at the Swiss Light Source (SLS) at PSI to decipher the structure of the CCR7 receptor and its corresponding chemokines. Meanwhile, Roche developed its own new protein-modifying technology modules, or crystallisation chaperones, to hasten the process.
With these, the researchers wereable to identify a suitable molecule that blocks the receptor and prevents a signal from being transmitted into the cell.
“Our experiments show that the artificial molecule, inside the cell, binds to the receptor. This keeps the chain reaction that leads to cell migration from getting started,” explains PSI’s Steffen Brünle.
Roche scientists then used computer simulation to search for fitting agents that could block the signaling protein – five compounds were determined as possible candidates for cancer therapy and one of them is already being tested as a potential drug against metastasis.
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