Heart disease and cancer are the leading causes of death in the United States, but it is rare that cancer makes its way to the heart.
It’s an observation that clinicians have been grateful for, though largely unable to explain. But in a paper published Thursday in Science, researchers propose one potential explanation: The constant pressure that the organ is under from beating thousands of times a day and pushing gallons of blood creates an environment that is hostile to cancers. The study, which was conducted in mice, is preliminary, but outside experts said it points to potential new approaches for cancer treatments.
“It’s interesting that [cancer] doesn’t occur that often in the heart. People have not really been sure exactly why, but it’s just something that we accepted. What makes this article really fascinating is that they have provided a potential mechanism to explain this phenomenon,” said Michael Fradley, a professor of clinical medicine at Johns Hopkins University who was not involved with the study.
In some ways, it is counterintuitive that the heart would not be prone to metastatic cancers, because cancer cells are carried around the body through the bloodstream. “This is certainly incredibly interesting — it’s hypothesis generating, which is exciting, and I’m really enthusiastic about the foundation that this creates for future studies,” Fradley said.
It has long been documented that heart cells have a limited ability to regenerate themselves, which is often a problem for patients with severe heart failure. Researchers suspected that this lack of regenerative capacity could be responsible for a lack of cancer, a disease of runaway regeneration, originating in the heart. Even when metastatic cancers make their way to the heart, they tend to be smaller than cancers in other organs.
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The authors of the new study, led by by Giulio Ciucci and Serena Zacchigna at the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, were inspired to see if there was a connection to mechanical stress because of earlier observations that cellular regeneration occurs in patients implanted with a left ventricular assist device, a mechanical pump that takes pressure off their failing heart.
To test their hypothesis, the researchers transplanted a second heart into mice that was not pumping blood through the left ventricle. They then injected cancer cells into both hearts and found that cancer spread quickly in the transplanted heart, which was under less stress, but cancer rarely spread in the native heart.
The team also found genetic differences between cancers that were able to spread in the heart and those that were not, and identified a protein that senses mechanical forces and reduces the activity of genes linked to proliferation in cancer cells. “What’s really striking is this link they provide between mechanical load and epigenetic regulation. They show that these physical forces can directly alter gene expression in cancer cells, which is a powerful concept that extends beyond cardiology,” said Javid Moslehi, a cardiologist at the University of California, San Francisco, who was not involved in the study.
Another potential treatment route the study opens up is using machines to massage cancer cells, imitating the rhythmic beating of the heart. It’s a line of research the study’s authors are pursuing now, said Zacchigna, a molecular biologist and physician. They have partnered with engineers to create devices that could sit on the skin, applying pressure to cancers that are relatively close to the surface, like skin or breast cancers.
“We have the first prototypes, and results are promising,” she said, adding that the team hopes to explore how this therapy could bolster other kinds of treatment as well. “Other than adding this mechanical stimulus, it is a way to perform a kind of massage the tumor that could improve the delivery of any chemo or immunotherapy.”
