Researchers from the University of Turku in Finland and the Gustave Roussy Institute in France have identified a molecular mechanism that explains how an aggressive form of colorectal cancer spreads to the abdominal cavity. Published in Nature Communications, the study focuses on mucinous colorectal adenocarcinoma, which accounts for approximately 10 to 15 percent of all colorectal cancers and is more frequently diagnosed in younger adults and women.
Understanding Mucinous Colorectal Adenocarcinoma
Unlike typical forms of the disease, mucinous colorectal adenocarcinoma spreads as compact clusters of cells known as tumour spheres that travel to the peritoneum. These tumour spheres can adopt an inverted structure where mucus forms a protective outer layer. According to Academy Professor Johanna Ivaska from the University of Turku, this specialized structure helps tumour cells migrate, invade surrounding tissues effectively, and exhibit greater resistance to chemotherapy.
Molecular Chain Reaction and Therapeutic Potential
When these tumour spheres contact collagen, they trigger a molecular chain reaction involving three proteins: SorLA, HER2, and HER3. This biochemical process causes the tumour cells to return to a conventional state, thereby strengthening their attachment to surrounding tissue. Analysis of patient samples confirmed that SorLA, HER2, and HER3 levels were higher in conventional tumour spheres than in inverted ones.
To explore potential interventions, researchers tested therapeutic antibodies targeting the HER2 and HER3 receptors, which are already used in treating other cancers. Laboratory-grown tumour spheres treated with these antibodies experienced cancer cell death, were forced into inversion, and showed a reduced ability to attach to the peritoneum. Doctoral Researcher Meri Pelkonen noted that while the results indicate a potential method for slowing cancer spread, further research and clinical trials remain necessary.
Insights into ZFP36L2 and Cell Plasticity
In related insights on colorectal cancer metastasis, medical professionals have examined the role of the ZFP36L2 protein. Dr. Tanvi Singh, an oncologist at M|O|C Cancer Care and Research Centre in Karol Bagh, explained that the gut possesses a notable ability to repair damaged tissue, a process heavily involving the ZFP36L2 protein as part of an emergency repair program.
During tissue injury, ZFP36L2 allows differentiated cells to temporarily gain stem-like characteristics to participate in tissue renewal. However, disseminated colorectal cancer cells can exploit this exact mechanism to adapt to new environments, survive, and metastasise. Dr. Singh emphasized that cancer cells exhibit high plasticity, shifting states based on their surroundings. Although inhibiting ZFP36L2 might seem advantageous, experts caution that it is premature to consider it a viable therapeutic option due to the protein’s critical role in normal tissue repair and the risk that cancer cells might find alternative pathways to compensate.
Funding and Future Implications
The research conducted by the University of Turku and the Gustave Roussy Institute received financial backing from several organizations. Funding sources for the study included the Cancer Foundation Finland, the Research Council of Finland, the Sigrid Jusélius Foundation, and EU Horizon 2020.
Researchers believe that identifying these underlying biological behaviors and mechanisms will eventually support the development of new treatment approaches. Furthermore, these discoveries could aid clinicians in identifying patients at high risk of peritoneal metastasis before aggressive symptoms fully manifest.
