In lab, mucus-coated tumor spheres expose colon cancer targets

A white coat of mucus surrounds a compact cluster of colorectal cancer cells as it moves across the peritoneum. When the cluster reaches a new site, the mucus shifts inward and the cells attach more firmly to surrounding tissue. Researchers from the University of Turku in Finland and the Gustave Roussy Institute in France have traced the molecular switch behind that change in mucinous colorectal adenocarcinoma.

This aggressive form represents around 10%–15% of all colorectal cancers and is more common in young adults and women. Unlike most colorectal tumors, it spreads as small clusters called tumor spheres. On the peritoneum—the tissue lining the abdominal cavity—those clusters can establish new growths, a pattern associated with poor prognosis and limited treatment options.

The team found that contact with collagen, the structural protein in connective tissue, starts a multistep reaction. Levels of three proteins—SorLA, HER2 and HER3—rise in the cancer cells. Their activity changes the sphere from an inverted state, with mucus on the outside, to a conventional state, with mucus inside. At the same time, integrins—cell receptors that grip surrounding tissue—attach more strongly. Patient samples showed the same pattern: conventional spheres had higher levels of the three proteins than inverted spheres.

That mechanism also suggests a possible treatment route. Antibodies targeting HER2 and HER3 already exist for other cancers, so the researchers tested them on tumor spheres grown in the laboratory. The treated cells began to die, became inverted and attached less effectively to the peritoneum. The result suggests a way to slow spread, but Doctoral Researcher Meri Pelkonen and her colleagues say further research and clinical trials are still needed.

And what does it change, concretely? The mechanism could help clinicians identify patients whose tumors are more likely to spread to the abdominal cavity, while giving researchers targets for future treatments. It does not yet show that the antibodies prevent metastasis in patients: the reported effects come from laboratory tests and patient-sample analysis, not a clinical trial.