Cooperative Research Networks Oriented to Health Results (RICORS)
26 July 2024
Tumor suppressor genes as potential therapeutic targets
31 July 2024The findings of the team of researchers from the Federal Institute of Technology in Zurich will help develop treatments that could slow down the metastasis process.
A new work has managed to demonstrate how colorectal cancer cells colonize the liver. This is a work by a team of researchers led by Andreas Moor at the Department of Biosystems Sciences and Engineering at the ETH Zurich (Basel) published in the journal Nature, whose findings will help develop treatments with which the metastasis process could be stopped.
Cancer is said to metastasize when cells from the primary tumor break away and travel through the circulatory system to other parts of the body. «Colorectal cancer metastasizes to the liver because of the way our blood flows«says Moor. The blood is first enriched with nutrients in the intestines before reaching the liver, which metabolizes the nutrients. For colorectal cancer cells, the liver is the last stop. "They become trapped in the capillary network of the liver."
«Colorectal cancer metastasizes to the liver because of the way our blood flows»
Andreas Moor. Researcher at the Department of Biosystems Sciences and Engineering at the Federal Polytechnic School of Zurich.
PhD student Costanza Borrelli and other members of Moor's team have shown that liver cells also play an important role in whether cancer cells lodged there can colonize their new location. Science has known for more than a century that, like plant seeds in the soil, cancer cells depend on their environment, but until now it was unknown what molecular mechanisms are involved in this process.
Through sophisticated tests using genetically modified mice, Moor and his team have discovered that The secret lies in certain proteins on the cell surface. When liver cells have a protein called Plexin-B2 and colorectal cancer cells have certain proteins in the semaphorin family, colorectal cancer cells can adhere to liver cells.
It should be noted that cancer cells that have semaphorins on their surface are especially dangerous, as attested to by the clinical studies cited by the Moor researchers in their article. Study data show that colorectal cancer produces metastases earlier and more frequently in the liver if the tumor has large amounts of semaphorins.
Plexin and its counterpart, semaphorin, were already known to the scientific community for their role in the nervous system, where both proteins direct the growth of nerve cells and ensure that they form the appropriate pathways. “It is not at all clear why liver cells also create plexin and what this protein does in healthy livers, and we are very interested,” says Moor. In other words, The question of its function remains open.
"It is not at all clear why liver cells also create plexin and what this protein does in healthy livers, and we are very interested"
Andreas Moor. Researcher at the Department of Biosystems Sciences and Engineering at the Federal Polytechnic School of Zurich.
However, what Moor and his team have discovered is that direct contact between plexin and semaphorin triggers fundamental changes in colorectal cancer cells. To separate from the primary tumor, cancer cells have to change their identity: They break free from the intestine's surface layer, or epithelium, and sever their tight connections with neighboring cells.
Once in the bloodstream, cancer cells look like connective tissue called mesenchyme. However, once they find their new niche, thanks to plexin present in some liver cells, cancer cells return to their sedentary form. «A process of epithelialization occurs"the researchers wrote in their article. Moor expands: "This can be detected immediately if you look at the cancer cells, since they form invaginations similar to the folds or crypts of the intestines."
The researchers' discovery will not only affect colorectal cancer patients: other studies have shown that Plexin also promotes metastasis formation in melanoma and pancreatic cancer. For Moor and his team, this raises many new questions. One of them is the following: when cancer cells group together to form a tumor, they also influence the cells in their environment. "Cancer cells create their own ecosystem," explains Moor.
«Cancer cells create their own ecosystem»
Andreas Moor. Researcher at the Department of Biosystems Sciences and Engineering at the Federal Polytechnic School of Zurich.
If efforts to inhibit the crucial interaction between plexin and semaphorin are successful, cancer may be prevented from generating new tumors. This is because in the early phases, when the relationships between the cells of this ecosystem have not yet been firmly established, tumor metastases are especially vulnerable, explains Moor. He seems certain that the answer lies in this "critical period of time in the development of metastases," although the road to a possible treatment is still long.
Source: Heraldo de Aragón
Image: Metastasis of colorectal cancer (left half of the image) in the liver. | ETH ZURICH / Morgan Roberts, ELE