new discovery may help researchers stop skin cancer from spreading
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sun exposure is one of the leading risk factors for developing skin cancers like melanoma.
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a new study has shed light on how the quick-spreading skin cancer, melanoma, is able to infiltrate other areas of the body. this finding may allow researchers to reverse the process and make all forms of the disease less deadly.
the research, published in nature communications, focused on melanoma, a form of cancer that can usually be cured if it is detected early enough. if skin cancer cells have a chance to break away from the original tumour and move to other areas of the body, however, it becomes much more difficult to treat.
“we’re still not targeting the secondary disease enough in the clinic and i think we need to change this,” said victoria sanz-moreno, lead author of the study at barts cancer institute, queen mary university of london. “in our lab, we want to understand: what are the characteristics of cells that are able to metastasize? what are their weaknesses? and how do we target them?”
an estimated 9,000 canadians were diagnosed with melanoma, the most serious form of skin cancer, in 2022, according to the canadian cancer society. the disease, which originates in the skin’s melanocyte cells, can lead to cancerous tumours capable of destroying surrounding tissue and spreading to other parts of the body. roughly 1,200 canadians were projected to die from the disease in 2022, with 54 per cent of diagnoses and 64 per cent of deaths occurring in men.
by using a special model that allowed them to view migrating cancer cells in three dimensions, researchers discovered that metastasizing cells essentially alter their energy systems to quickly facilitate their journey to other areas of the body. these cells were also able to adjust their structure to allow a form of movement known as rounded-amoeboid migration. by maintaining a loose connection to their surroundings, they are able to slither their way deeper into the body’s tissues.
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this form of motion requires less energy and, as a result, metastasizing cells reshape their mitochondria into many smaller pieces that operate in low-power mode, as opposed to normal cells with larger mitochondria that operate in high-power mode.
“these metastatic cells are rewiring themselves to be very efficient,” said eva crosas-molist, researcher at barts cancer centre and first author on the paper. “they only need low levels of energy to move, which helps them to survive in the potentially stressful environments they are migrating to, where there may be a lack of nutrients or oxygen.”
the team found if they manipulated the multiple mitochondria in these cells to join together, it halted their invasive behaviour. similarly, when they divided the mitochondria found non-invasive cells, they began to mimic the behaviour of metastatic tumour cells. the also discovered that a protein known as ampk oversees this process, determining the energy needs of a cell and controlling its cytoskeleton, which governs how it moves and acts.
“that was a really surprising thing for us — we wouldn’t have imagined that changing the mitochondria could affect the cytoskeleton and vice versa,” sanz-moreno said. “by modifying these little mitochondria, you create a global change, altering what the cell looks like and its whole behaviour.”
the team hopes these discoveries will prove essential in creating new therapies for all forms of cancer. “patients whose cancer has spread often face tougher treatments and lower chances of survival,” said ketan patel, chief scientist at cancer research u.k., the organization that funded the research. “these insights about how cancer cells travel around the body could be incredibly valuable for designing interventions to prevent this in the future. the more we know about what’s happening in the bodies of people with cancer, the greater our ability to tackle it will be.”
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dave yasvinski is a writer with healthing.ca
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