According to a new study, heartbeats change the way cancer cells function, inhibiting their ability to multiply and spread.
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This may explain why heart cancer is so rare, with just 2 in 100,000 people developing it annually.
A protein known as Nesprin-2 is key to this phenomenon. It is located in the outer membrane of the cell nucleus and is already known to sense and respond to mechanical forces. It now appears that Nesprin-2 senses the heartbeat and stops cancer cells from multiplying.
In addition to offering a possible explanation for why heart cancer is so rare, the findings could pave the way for new treatments for other types of cancer, the researchers concluded in the study published April 23 in the journal Science. The mechanical load of heartbeats, or the physical force they exert, has been found to limit the ability of heart tissue to regenerate. So the scientists wanted to see if heartbeats could also prevent cancer cells from multiplying.
First, they implanted lung cancer cells into the hearts of laboratory mice to observe their growth and spread. The hearts were either beating normally or “unloaded,” meaning connected to a blood supply but not actively pumping. The beating hearts appeared to inhibit cancer growth, while the unloaded hearts showed massive proliferation of cancer cells.
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The team performed a similar experiment on rat heart tissue grown in laboratory dishes. They found that changing the mechanical load on the tissue affected the behavior of lung cancer cells; the cancer grew and spread more when the mechanical load was reduced.
To understand what causes this phenomenon, the researchers took tissue samples from human patients whose lung, colon or skin cancer had spread to the heart and other organs. They mapped the gene activity of these cancer cells and focused on their epigenetics, the “marks” on DNA that regulate which genes are turned on.
They found that certain epigenetic markers are linked to tumor growth and confirmed that heart beats reduce these markers. They then identified the protein Nesprin-2 as a key player — when they turned off Nesprin-2 in beating heart tissue, they saw an increase in tumor cell proliferation.
These findings are the first to show that mechanical forces beyond the tumor itself influence the growth and spread of cancer cells. The ability of mechanical forces to inhibit cancer proliferation also appears to be a general mechanism, as this feature has been observed to be common to many types of cancer.
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The potential for harnessing mechanical stimulation in cancer therapies is an exciting idea to explore. However, a deeper understanding of how the properties of the tissue surrounding cancer cells affect their ability to perceive mechanical forces is needed.
