Researchers from the University of Turku in Finland and the Gustave Roussy Institute in France have uncovered a molecular mechanism that may help identify colorectal cancer patients whose tumors are more likely to spread to the abdominal cavity. The findings, published in Nature Communications, could eventually help doctors better assess metastatic risk and explore new treatment strategies.
The study focused on mucinous colorectal adenocarcinoma, an aggressive form of colorectal cancer that accounts for roughly 10% to 15% of colorectal cancer cases. It is also more common among younger adults and women than some other forms of the disease.
Tumor cells can change their structure
Unlike many colorectal cancers, mucinous tumors can spread through small clusters of cancer cells known as tumor spheres. These clusters can travel to the abdominal cavity and eventually form tumors on the peritoneum, the membrane lining the abdominal cavity.
Researchers found that these tumor spheres can exist in two different structural states: conventional and inverted.
In the inverted state, cancer cells release mucus around the outside of the tumor cluster. This mucus can form a protective layer around the cancer cells, potentially making them more resistant to chemotherapy while also helping them move through the abdominal cavity.
When the tumor spheres reach the peritoneum, however, some can switch back to a conventional state. This allows them to attach more firmly to surrounding tissue, a process that may contribute to the development of peritoneal metastases.
Researchers identify a molecular chain reaction
The team investigated what causes this structural change. They found that when tumor spheres interact with collagen, a structural protein found in connective tissue, a series of molecular signals is activated.
This process increases the levels of three proteins: SorLA, HER2 and HER3. Together, these proteins help cancer cells return to the conventional state and strengthen the activity of integrins, receptors that help cells attach to surrounding tissue.
Analysis of patient tumor samples supported the laboratory findings. Tumor spheres in the conventional state showed higher levels of SorLA, HER2 and HER3, while inverted tumor spheres had lower levels of these proteins.
Existing drugs may offer a potential clue
The discovery could also point toward possible treatment approaches. Because therapies targeting HER2 and HER3 already exist for certain cancers, researchers tested whether these antibodies could influence the behavior of the tumor spheres.
In laboratory experiments, treatment caused cancer cells to die, altered their structure and reduced their ability to attach to the peritoneum. These results suggest that targeting this pathway could potentially interfere with the spread of mucinous colorectal cancer.
However, the researchers stress that these findings are still experimental. More research and clinical trials will be needed before such an approach could become part of routine cancer treatment.
Could this help predict metastatic risk?
One of the most important implications of the research is the possibility of identifying patients whose tumors are more likely to spread into the abdominal cavity.
Understanding the molecular features associated with tumor-cell inversion could eventually help doctors recognize cancers with a higher metastatic potential. It could also provide researchers with new targets for developing treatments designed to prevent or slow the spread of disease.
Colorectal cancer remains a major cause of cancer-related illness and death worldwide. The growing incidence of colorectal cancer among younger adults has also increased interest in understanding why certain tumors behave more aggressively.
For now, the new findings represent an important step in understanding how mucinous colorectal cancer spreads. They do not yet provide a clinical test or proven new treatment, but they offer researchers a clearer picture of the biological processes that may allow aggressive cancer cells to invade new tissues.
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