Mucus-coated tumor spheres reveal potential targets to curb colorectal cancer spread

Researchers from the University of Turku in Finland and Gustave Roussy Institute in France have uncovered a molecular mechanism that controls whether cells in aggressive colorectal cancer are conventional or inverted as they spread throughout the body. This finding could help identify patients at higher risk of the cancer spreading to the abdominal cavity.

The study, published in Nature Communications, focused on mucinous colorectal adenocarcinoma, a rare but aggressive form of cancer that accounts for 10%–15% of all colorectal cancers. Unlike typical colorectal cancers, mucinous colorectal adenocarcinoma spreads as small, compact clusters called tumor spheres. These spheres migrate to the abdominal cavity and spread on the peritoneum, leading to a poor prognosis and limited treatment options.

Inverted tumor spheres, where the mucus layer forms on the outside of the cell cluster, are associated with a worse prognosis and increased resistance to chemotherapy. However, when tumor spheres reach the peritoneum, some revert to a conventional state with the mucus layer inside the cluster, which helps the cells adhere to surrounding tissue.

The researchers discovered that contact between tumor spheres and collagen, a protein found in connective tissue, triggers a series of events that increase levels of three proteins—SorLA, HER2, and HER3—in cancer cells. These proteins cause the tumor cells to revert to the conventional state and strengthen their attachment to the peritoneum.

Therapeutic antibodies targeting HER2 and HER3 receptors, which already exist and are used in treating other cancers, were found to induce cell death, promote inversion, and reduce peritoneal adhesion in laboratory models. This suggests that these drugs could potentially slow the spread of cancer. However, more research and clinical trials are needed to confirm these findings.