An international team of scientists, including Leiden professor Hermen Overkleeft, has discovered a molecule that prevents tumors from spreading from a primary cancer location to other parts of the body, according to the report. University of York in a press release.
The multidisciplinary research team, from the University of York, de university of Leiden and Technion (Israel Institute of Technology) found that the small, sugary molecule maintains the integrity of tissue around a tumor during cancer. They have shown that the sugary molecules significantly reduce cancer metastasis in mice, paving the way for development towards clinical application.
“Now we need to find out whether the compound is stable, safe for the human body, ends up in the right place in sufficient quantities, and so on, said lead author of the study, Professor Hermen Overkleeft of Leiden University. “It takes a few years, it can come to nothing and someone has to be willing to take that financial risk. Our molecule is one of the few agents that can tightly and specifically inhibit heparanase. Medicine has a preference for these kinds of small, simple molecules.”
sugars
Metastasis, the spread of cancer cells to other places in the body, is what makes cancer so deadly. The formation of metastases is dependent on the ability of cancer cells to detach from the primary tumor site and penetrate the walls of blood vessels and tissue barriers to reach secondary growth sites.
This metastatic invasion process requires biological molecules called enzymes that digest proteins and sugars in the space around the cells, allowing the cancer cells to pass through the resulting openings. An abundant class of sugars that surround cells are the heparan sulfates, long chain-like molecules that help stabilize the integrity of the extracellular space.
Heparan sulfate sugars are digested by an enzyme called heparanase, which breaks up the “chains” and thereby weakens the space around the cells. Metastatic cancer cells produce large amounts of the enzyme heparanase, which helps them spread throughout the body. Inhibiting heparanase is therefore an important target for anti-cancer therapy.
Inaccessible
The researchers developed and tested a new sugar-like molecule that reacts with the enzyme heparanase, whose 3-D structure was first solved by the scientists. Once the new molecule is bound, the heparanase enzyme can no longer bind or cut the heparin sugar chains around cells. In this way, the tissue around the cells remains firm and inaccessible to dislodged cells. In York, Professor Gideon Davies and Dr Liang Wu from the Department of Chemistry demonstrated how the enzyme inhibitor inhibits heparanase. The research team is now looking at how the molecule can be further improved.
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Promising
Professor Davies: “It’s fantastic to see the work progress from fundamental studies of the structure and function of enzymes to small molecules with potent anti-cancer activities. It’s really exciting”
Technion researchers have studied the new molecule in mouse models of lung cancer, breast cancer and blood cancer. Although it is still too early to determine whether the new molecule will be used clinically, the results are promising and the involved institutes have already applied for a patent on the molecule.
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