In a malignant tumor, over time, cells appear that leave it, going to wander throughout the body along with the blood. Having settled somewhere, they will become the founders of a metastasis, a secondary tumor. However, metastatic cells settle in different places; they have certain preferences. For example, secondary tumors often appear in the bones. A particularly strong predilection for bones is shown by wandering cells emerging from prostate or breast tumors; Moreover, among bones they often prefer vertebrae. Any cell, healthy or malignant, depends on its microenvironment, that is, on other cells around. Apparently, malignant cells really like the microenvironment in bones in general and in the vertebrae in particular. Employees Cornell University described in Naturewhat exactly they like there.
Bone cells, like the cells of any other organs, originate from stem precursors, due to which tissues and organs are gradually renewed. The peculiarity of bones is that they contain a whole set of stem cells. For example, in tubular bones (which include the femur, tibia, ulna, radius, etc.) there are rounded ends – the epiphyses and a long part between them – the metaphysis. Where the long part is adjacent to the rounded part, there is a so-called growth plate: its cells ensure the growth of bones in length. The bone is also covered with periosteum, and it is also renewed by special stem cells. There is a cavity inside the tubular bones, and it is lined with a layer of connective tissue similar to periosteum – but this “internal periosteum” (or endosteum) is again renewed by its own cells.
The researchers hypothesized that vertebrae contain stem cells that are different from their counterparts in long bones. And perhaps vertebral stem cells have some peculiarities that cause wandering malignant cells to travel to the vertebrae. And now in the vertebrae we were able to find stem cells whose gene activity is not similar to the gene activity of other bone stem cells. These cells differ from others in genes ZIC1 and PAX1, encoding proteins-transcription factors – that is, they control the work of other genes. Manipulating activity ZIC1 and PAX1, the researchers became convinced that the stem properties of a new group of cells really depend on them. In turn, by regulating the activity of these cells in mice, it is possible to influence the growth of vertebrae, but not long bones. That is, the new bone stem cells found in the vertebrae helped only the vertebrae grow and renew themselves.
And they also serve as bait for metastatic cells. The newly discovered stem cells secrete a lot of the protein MFGE8, which attracts wandering malignant cells and stimulates their division. (One of the functions of MFGE8 is to help cells connect to each other and stay together; it may have other properties that cancer cells use to their advantage.) The attraction of malignant wandering cells to the vertebrae is due specifically to vertebral stem cells and their MFGE8, and not by any features of blood flow or the structure of the blood vessels supplying blood to the vertebrae. This has been shown both in experiments on mice and in experiments with bone organoids – tiny replicas of bones grown from stem cells in the laboratory. The same stem cells are found in human vertebrae, and vertebral organoids grown from human stem cells also attracted tumor cells. That is, we can say with a high degree of confidence that a new type of bone stem cells, discovered in the vertebrae, serves as a bait for metastatic cells, and they attract them not only in mice, but also in people.
Here it is necessary to clarify that the malignant cells in the experiments were breast cancer cells. Breast cancer, as stated at the beginning, really likes to metastasize to the vertebrae. It would be interesting to see other types of cancer – how they react to these new stem cells of their MFGE8 (by the way, the MFGE8 protein is synthesized not only by them, but also by some other bone cells). As for practical medical implications from the new results, they will obviously appear when we learn more about the interaction of cancer cells with bone stem cells and their proteins.
Source: Автономная некоммерческая организация "Редакция журнала «Наука и жизнь»" by www.nkj.ru.
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