Is head trauma the cause of brain cancer?
Improper tissue healing stimulated cancer
Maria Krivochenko, Naked Science
The picture shows how incorrect tissue healing leads to the formation of a brain tumor / ©Nature Cancer
The study was conducted by a team from the University of Toronto in Canada, SickKids Hospital for Children and the Princess Margaret Cancer Center. Scientists have applied the latest technologies of single-cell RNA sequencing and machine learning. So they identified the molecular composition of glioblastoma stem cells (GSCs), which are responsible for the appearance of tumors and relapses after treatment. The results are published in the journal Nature Cancer.
The team collected HSCs from the tumors of 26 patients – about 70 thousand in total – and examined them in the laboratory. The analysis revealed new subpopulations of HSCs that carry molecular signs of inflammation and mix with other cancer stem cells inside patients' tumors.
This suggests that some glioblastomas begin to form when the normal process of tissue healing is disrupted by mutations. This can happen many years before patients develop symptoms. As soon as the mutated cell begins to participate in wound healing, it cannot stop multiplying, and this stimulates the growth of the tumor, the scientists explained. Thus, the data confirmed that each tumor contains several subpopulations of molecularly different cancer stem cells.
"Our data show that correct mutations in brain cells can be disrupted due to traumatic brain injuries and incorrect tissue healing. As a result, this leads to the appearance of cancer," said Dr. Peter Dirks, co–author of the study.
In addition, it turned out that each tumor can be in one of two molecular states, called "development" and "reaction to damage", or on the border between them.
The state of development is a distinctive feature of glioblastoma stem cells, it resembles the state of rapidly dividing stem cells in the growing brain before birth. The second condition showed increased regulation of immune pathways and markers of inflammation, such as interferon and TNFalpha, which indicate wound healing processes.
Experiments have shown that the analysis of these conditions helps to identify a number of therapeutic targets that scientists have not considered before. It also turned out that the intersection of these conditions is individual for each patient: therefore, the results of the study can be used to develop individual therapy.
"Now we will look for drugs that are effective for any patients, regardless of the condition of their tumors,– said Dr. Trevor Pugh, one of the leaders of the study. "Now we have a real opportunity to dissect just one tumor cell and, thanks to it, create a drug cocktail that can remove cancer stem cells."
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