Hospital del Mar discovers why colon cancer metastasizes to the liver

BarcelonaOne of the biggest challenges for the cancer research community is the disease's ability to spread to new parts of the body. This is metastasis, a complex process that causes many cancer deaths, making it a key focus for researchers worldwide, especially those dealing with the most common tumors. This is the case, for example, with colorectal cancer, the third most frequently diagnosed cancer globally. Now, a team from the Hospital del Mar Research Institute has identified a mechanism that may explain how this cancer metastasizes to the liver. Specifically, they found that the absence of a particular protein allows tumor cells to cluster, migrate, and reproduce the tumor in the liver.

The study, published this Friday in the journal Nature CommunicationsThe study demonstrates that the immune system is capable of eliminating tumor cells when they migrate individually from the colon to the liver. Conversely, when tumor cells cluster together, they are able to evade the body's defenses and colonize a new organ. The role of the protein IKKα is key to this process, as cells are only able to cluster and survive migration when this protein is absent. "When this protein is missing, the junctions are stronger, and the cells form much more efficient groups for metastasis," explains Lluís Espinosa, lead author of the study and coordinator of the research group on molecular mechanisms of cancer and stem cells at the center.

To conduct this study, researchers used artificial organs created in the laboratory from stem cells called organoids. These were developed from cells of colon cancer patients in which IKKα had been removed. The researchers then conducted the study in mice and demonstrated the existence of a specific population of tumor cells that bind to each other very robustly and are responsible for generating metastases in the liver. The absence of the protein under study was very pronounced in this population, which, according to the authors, explains why tumors with lower levels of IKKα have a greater metastatic capacity.

Early detection

The work now continues with patient samples, with whom the authors will try to replicate the results obtained. The team is confident that their findings will lead to the development of prognostic markers for colon cancer patients in the near future, and even a way to treat metastasis. "We are confident that our results can contribute in the future to identifying patients at higher risk of developing metastasis and, eventually, open the door to new therapeutic strategies aimed at preventing it," explains Espinosa.

Early detection is another key element in the fight against the disease. The Ministry of Health and the regional health departments approved [a plan/method] at the end of the year Extend colorectal cancer screening to age 74A program for the early detection of these tumors, previously aimed at the 50-69 age group, is now available. People at potential risk of developing the disease—the main risk factor being age—receive a letter at home or a text message encouraging them to participate in the screening. The message includes a list of pharmacies where they can pick up the [test/resource/etc.].kitTo take the test at home. The system is simple: collect a stool sample with a swab, store it in a tube –all materials are provided by the pharmacy– and take it to one of the centers on the list for analysis. This will determine if there are signs that could cause cancer (precancerous lesions) or if a positive diagnosis has already been made. If the result is negative, it is important to participate every two years –participants in the screening receive a follow-up letter– to ensure that there has been no progression to a tumor.