Heart disease and cancer are the leading causes of death in the United States, but cancer rarely progresses to the heart.
This is a finding that clinicians appreciate, but it is largely inexplicable. But in a paper published Thursday in the journal Science, researchers propose one possible explanation. The theory is that the organs are under constant pressure as they beat thousands of times a day and pump out gallons of blood, creating an environment ripe for cancer. Although the study, conducted in mice, is preliminary, outside experts said it points to a potential new approach to cancer treatment.
“What’s interesting is that (cancer) doesn’t occur as often in the heart. People don’t really know why exactly, but we just accepted it. What’s really interesting about this paper is that they provide a possible mechanism to explain this phenomenon,” said Michael Fradley, a professor of clinical medicine at Johns Hopkins University who was not involved in the study.
In some ways, it’s counterintuitive that the heart is less susceptible to metastatic cancer, since cancer cells are carried through the body through the bloodstream. “This is certainly very interesting. This is hypothesis-generating and exciting. I’m really excited that this will lay the foundation for future research,” Fradley said.
It has long been established that heart cells have a limited ability to self-renew, which is often a problem for patients with severe heart failure. The researchers suspected that this lack of regenerative ability could be responsible for the lack of cancer, a runaway regenerative disease that originates from the heart. Even when metastatic cancer reaches the heart, it tends to be smaller than cancers in other organs.
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The authors of the new study, led by Giulio Ciucci and Serena Zacchinha at the International Center for Genetic Engineering and Biotechnology in Trieste, Italy, were inspired to investigate whether there was a link to mechanical stress by previous observations that cell regeneration occurred in patients implanted with left ventricular assist devices, mechanical pumps that take pressure off a failing heart.
To test their hypothesis, the researchers implanted mice with second hearts that were no longer pumping blood from the left ventricle. They then injected cancer cells into both hearts and found that the cancer spread rapidly in the transplanted heart, which was under less stress, whereas the cancer spread almost never in the native heart.
The researchers also discovered genetic differences between cancers that can spread to the heart and those that don’t, and identified a protein that senses mechanical force and reduces the activity of genes associated with cancer cell growth. “What’s really surprising is this link they create between mechanical loads and epigenetic regulation. They show that these physical forces can directly alter gene expression in cancer cells. This is a powerful concept that extends beyond cardiology,” said Javed Moslehi, a cardiologist at the University of California, San Francisco, who was not involved in the study.
Another potential treatment route opened up by this study is the use of machines to massage cancer cells by mimicking the rhythmic beating of the heart. Zacchinha, a molecular biologist and physician, said this is a line of research that the study authors are currently conducting. They worked with engineers to develop a device that can be placed on the skin to apply pressure to cancers that are relatively close to the surface, such as skin cancer or breast cancer.
“We have the first prototype and the results are promising,” she said, adding that the team wants to study how the therapy can enhance other types of treatments. “Besides applying this mechanical stimulation, it’s a way to give the tumor a kind of massage, which can enhance the effectiveness of chemotherapy or immunotherapy.”
