They have discovered how to prevent cancer cells from entering the liver

To separate from the primary tumor, cancer cells must change their identity.

One of the problems a person faces when colorectal cancer is detected is that if it is not diagnosed in the early stages, it can cause liver metastases. For years, scientists have been studying how to stop these episodes, which can become severe over time.

Thus, the work of a group of researchers led by Andreas Moor in the Department of Science and Technology Biosystems at ETH Zurich (Basel) published in the journal Natureconcluded that recent discoveries about how to stop liver colonization could help develop new treatments.

“Colorectal cancer metastasizes to the liver because of the way the blood flows,” Moore notes. The blood first picks up nutrients in the intestines, then travels to the liver, where the nutrients are metabolized. For colorectal cancer cells, the liver is the last stop. “They end up in the capillary network of the liver.”

Using sophisticated tests using genetically modified mice, Moore and his team found that the secret lies in certain proteins on the cell’s surface

When liver cells contain a protein called plexin-B2 and colorectal cancer cells contain certain proteins in the semaphorin family, colorectal cancer cells can attach to liver cells.

The researchers’ discovery won’t just affect colorectal cancer patients: Other studies have shown that plexin also promotes metastasis in melanoma and pancreatic cancer. For Moore and his team, this raises a host of new questions. One is this: When cancer cells cluster together to form a tumor, they also influence the cells in their surroundings. “Cancer cells create their own ecosystem,” Moore explains.

How Cancer Spreads

Moore and his team found that direct contact between the substances plexin and semaphorin causes fundamental changes in colorectal cancer cells. To break away from the primary tumor, cancer cells must change their identity: They break out of the surface layer of the intestine, or epithelium, and sever their tight ties to neighboring cells.

When they enter the bloodstream, cancer cells look like connective tissue called mesenchyme. However, once they find their new niche, thanks to a substance called plexin present in some liver cells, the cancer cells revert to their sessile form. “A process of epithelialization occurs,” the researchers write in their paper. Moore expands: “This can be seen immediately when you look at the cancer cells because they form invaginations similar to the folds or crypts of the intestine.”

New tumors can be avoided

If efforts to inhibit the crucial interaction between plexin and semaphorin are successful, cancer may be able to prevent new tumors from forming. This is because in the early stages, when the relationships between the cells of this ecosystem are not yet firmly established, tumor metastases are particularly vulnerableexplains Moore. He seems confident that the answer lies in the “critical period of metastasis development,” although the road to a possible cure is still a long way off.