Skin cancer cells produce “molecular drills” to penetrate healthy tissue and spread throughout the body, according to research that raises the possibility of new therapies for the disease.
The researchers used robotic microscopy to capture the formation of the drills by melanoma cells that were being grown on 3D skin-like material in the lab.
The drills help tumor cells attach to and punch holes in surrounding cells and structures, allowing the cancer to move beyond the site where it forms and reach other tissues and organs.
“This is the first time that this type of cell shape change has been associated with any type of metastatic cancer,” said Chris Bakal, professor of cancer morphodynamics at the Institute of Cancer Research in London.
Rates of melanoma have more than doubled in the UK since the 1990s, with more than 16,000 people newly diagnosed with the disease each year. In the early stages, surgeons can often remove the tumors, but the cancer becomes more difficult to treat as it spreads to other parts of the body.
Bakal and his colleagues grew melanoma cells in a 3D matrix rich in collagen, one of the main proteins found in the skin. By knocking out the genes in the cancer cells one by one, they discovered a particular gene, ARHGEF9, that was crucial to the formation of the molecular mock-ups.
The gene is found in all human cells, but in adults it is usually activated in brain cells to help them make new connections. Much earlier in human development, the gene allows neurons to produce their own drill-like structures, which help cells spread throughout the body and connect the nervous system.
Writing in the journal iScience, the researchers describe how disabling the ARHGEF9 gene in melanoma cells destabilized the molecular mechanisms so that the cancer could no longer attach to and burrow into neighboring tissues.
The finding raises hopes for new therapies for melanoma and possibly other cancers, such as neuroblastoma, that may spread in the same way. Although mutations in the ARHGEF9 gene are linked to a wide range of neurological disorders, the gene is thought to be more important during early development than in adulthood. If this is the case, developing drugs to inhibit the gene could block the spread of melanoma without serious side effects.
“We think that disarming the drill is likely to have widespread application,” Bakal said, though he suspects the process won’t be relevant to all melanomas. Because the gene is highly active in metastatic cells, and less so in many other normal cells, drugs that target it may be more selective for cancer cells and therefore less toxic, he said. add.
Beyond paving the way for future treatments, the work may have much broader implications for understanding cancer. “This work could ultimately change how we think about cancer cells and tumors. Specifically, neurons interact in large networks to form brains, speak via neurotransmitters, and propagate information through electricity,” said Bakal.
“Our work is showing that many cancer cells can act in a similar way to form these networks and that tumors could almost be ‘like the brain.’ Cancer cells connect to this network and transmit information to each other.” Further work in the laboratory suggests that cancer cells are electrically highly active.
Dr Sam Godfrey of Cancer Research UK said the results were encouraging. “These findings will allow future research to focus on the role of this target in melanoma and whether it could also help us beat certain cancers that affect children and young people,” he said. “Understanding more about the biology of this disease will lead to new tests and treatments for people with melanoma.”
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