How skin cancer becomes invasive
New research, the findings of which now appear in the journal Cell, has found a mechanism that allows aggressive forms of skin cancer to become invasive and spread quickly.
The study, which nonprofit organization Cancer Research UK funded, was conducted by a team from King’s College London and Queen Mary University of London (QMUL), both in the U.K.
In their experiment, they analyzed the makeup of skin cancer, or melanoma, cells, looking for the factors that work to their advantage.
They found that such cancer cells release certain molecules that interact with the immune system, sending out signals that favor the growth and spread of tumors.
In the future, the researchers hope that their new discovery will allow scientists to come up with better strategies for targeting aggressive melanoma and preventing a relapse.
A complex signaling mechanism
The research team looked both at melanoma tumor samples collected from human patients as well as mouse models of this form of cancer.
The investigation revealed that skin cancer’s aggressiveness is largely due to the presence of the protein myosin II in large quantities within cancer cells.
Myosin II contributes to cell motility, meaning that it helps cells move around; thus, high levels of this protein allow cancer cells to become more mobile and spread around the body quicker.
However, the researchers also found that myosin II stimulates the secretion of substances that send out signals to the immune system, “telling” it to bypass cancer cells.
More specifically, these substances “speak” to macrophages. These are specialized immune cells that normally consume and eliminate foreign bodies, malfunctioning cells, and cellular debris.
When these macrophages receive the signals from the melanoma cells — due to the action of myosin II — this “programs” them to avoid attacking cancer tumors, letting them grow and spread freely.
Targeting the chemical culprits
Another effect of the substances secreted thanks to myosin II is the puncturing of blood vessels so that cancer cells can pass into the bloodstream and travel to distant sites inside the body.
“This study,” explains lead author Prof. Vicky Sanz-Moreno, of QMUL, “highlights how cancer cells interact with and influence their surrounding environment to grow and spread.”
“Developing treatments that target the chemicals that alter the immune system,” she adds, “could help to prevent the spread of the disease.”
Further analyses showed the team that the most important chemical released through myosin II is interleukin 1A, a signaling protein that helped boost the invasiveness of cancer cells.
When the researchers decided to target myosin II and block its activity, cancer cells released less interleukin 1A — both in mouse models and human melanoma samples.
“By using therapeutic drugs that block either myosin II activity or the release of interleukin 1A, we can make the tumor less invasive and slow its growth, making it easier to treat.”
Prof. Vicky Sanz-Moreno
On the lookout for ‘treatment combinations’
The researchers explain that some drugs targeting myosin II activity already exist, but that people currently use them chiefly in the treatment of other conditions. These include glaucoma, an eye condition that tends to appear later in life and can lead to vision loss.
Prof. Sanz-Moreno and colleagues are now planning to test myosin II blockers in conjunction with current cancer treatments to see whether the two are compatible.
The option of using interleukin 1A inhibitors to reduce cancer cell invasiveness is also in sight; at present, there are clinical trials putting such drugs to the test for the treatment of colon cancer.
“We are excited to find out whether inhibitor drugs could be used in combination with other targeted therapies,” says Prof. Sanz-Moreno.
“By identifying effective treatment combinations,” she adds, “we hope that in the future myosin II and interleukin 1A inhibitors could be used to improve patient outcomes and reduce the risk of melanoma coming back.”
Prof. Richard Marais, director of the Cancer Research UK Manchester Institute, did not contribute to the study but notes that the new findings could lead to better methods of stopping melanoma from returning following traditional cancer therapy.
“When melanoma is removed, there’s always a chance that some cells could remain,” explains Prof. Marais, adding, “What this study shows is that we may be able to develop treatments to stop those remaining cells from spreading after surgery, helping patients to survive for longer.”
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