Updated:01/15/2020 10: 39h
Scientists of Sloan Kettering Institute, directed by the Spanish Joan MassaguéThey have discovered that the ability of cancers to metastasize to other organs depends on their ability to appropriate natural wound repair pathways. In a literal sense, metastasis would be a wound healing process that went wrong. These findings, published in the journal "Nature Cancer", provide a novel framework on the treatment of the same.
Metastasis is responsible for approximately 90% of all cancer deaths, although not much is known about what causes cancer cells to form metastases. Previous studies of the Massagué laboratory have shown that a molecule called L1CAM is necessary for numerous types of cancer cells to successfully metastasize in the organs. Normal healthy tissues do not usually produce L1CAM, but advanced cancers do. What exactly triggers the expression of L1CAM has so far been a mystery.
When observing human tumor tissues under a microscope, the researchers clearly observed that the division of L1CAM cells was more common in areas where an epithelial layer ruptured, that is, a wound occurred. Using a model of colitis in mice, the researchers confirmed that L1CAM is required for normal wound repair. Then, they wanted to know exactly why the wounds cause the cells to turn on the L1CAM. To find out, they turned to a recently developed technology called tissue organoids. Using these organoids, the researchers were able to demonstrate that separating the cells from their neighbors was enough to trigger the production of L1CAM.
Wounds are essentially a breach in the integrity of the epithelial layer of our skin: cells that are normally joined together to form a protective barrier suddenly separate. Similarly, in metastases, cells detach from their neighbors and adopt migratory behavior to reach new locations. The researchers suspect that the wound repair program equips both types of cells to survive this state without an anchor. In the first case, it allows the cells to move towards the gap and produce new tissues; in the second, it allows metastatic cells to separate and colonize new destinations.
As previous studies had already linked the expansion of cancer with wound healing, scientists wondered if the cells that produce L1CAM are necessary to start the growth of a primary tumor. Using a mouse model, they discovered that they were not: the tumors formed well without them. However, these L1CAM producing cells were necessary for tumors to metastasize. This led researchers to conclude that the stem cells that form primary tumors are different from those that form metastases.
This important study concludes that metastasis-initiating cells use the body's natural wound healing abilities to spread. In addition, these findings show that the stem cells that generate primary tumors are fundamentally different from those that generate metastases, suggesting that L1CAM is a promising therapeutic goal for the treatment of metastatic cancer.
"Now we understand metastasis as the regeneration of the wrong tissue – the tumor – in the wrong place – distant vital organs," explains Joan Massagué. «This is not just a metaphor. It is literally true in molecular and physiological terms, ”he concludes.