Scientists May Have Found Why Cancer Almost Never Spreads to the Heart

The beating heart may defend itself from tumors through the force of motion.

Cancer cells travel through the blood like restless seeds, searching for places to take root. Yet one organ they almost never conquer is the very pump that carries them around the body: the heart.

A new study offers a striking explanation. The heart may resist cancer because it never rests. Its constant squeeze and stretch appear to send a physical message to cancer cells, tightening control over growth genes and making the cardiac muscle a hostile place for tumors.

The work remains early and relies heavily on mice and engineered tissues, but it points to an unusual possibility whereby future cancer treatments might be heartbeat-inspired.

A Long-Standing Medical Oddity

Heart disease and cancer rank among the leading causes of death worldwide. But cancer of the heart remains extraordinarily rare.

This is weird.

The heart receives a rich blood supply, and cancer cells often spread through the bloodstream. By that logic, the heart should be a common landing place for metastases. Instead, tumors that begin in the heart are found in less than 1% of autopsies, and only a small fraction of cancers that start elsewhere spread there.

“It’s interesting that [cancer] doesn’t occur that often in the heart,” Michael Fradley, a professor of clinical medicine at the University of Pennsylvania who was not involved with the study, told STAT. “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.”

The new study, led by Giulio Ciucci and Serena Zacchigna at the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, began with a clue from heart biology. Soon after birth, mammalian heart cells mostly stop dividing. That loss of regeneration creates a problem after heart attacks or in severe heart failure, because damaged muscle cannot easily replace itself.

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But cancer is, in one sense, regeneration gone wild. Ciucci, Zacchigna and their colleagues asked whether the same forces that help stop adult heart cells from dividing might also stop cancer cells.

Mechanical Firewall

What happens when cancer is given a chance to grow in the heart?

In one experiment, the researchers in Italy used mice engineered to switch on cancer-promoting mutations in several organs, including the liver, heart, and skeletal muscle.

Tumors formed in different parts of the body, but the heart stayed cancer-free.

Then the team tried a more direct test. They gave mice a second heart, transplanted into the neck and connected to the bloodstream. This extra heart was alive and supplied with blood, but it was not doing the hard work of pumping blood through the body.

When the researchers injected cancer cells into both hearts, the cells grew quickly in the unloaded transplanted hearts. But in the animals’ own hearts, which kept beating under normal pressure, cancer cells struggled to spread.

The same pattern appeared in lab-grown heart tissue. When the tissue carried a normal mechanical load, cancer growth slowed. When that load was removed, lung, colon, and melanoma cancer cells grew more easily.

Altered Gene Expression

The study also showed how a heartbeat’s force might reach inside a cancer cell.

The trail led to a protein called Nesprin-2, which helps link the cell’s outer structure to the nucleus, where DNA is stored. That makes it one way for a cell to sense pressure, stretch, and movement.

When cancer cells were exposed to the normal force of a beating heart, Nesprin-2 became more active. The cancer cells then changed how they handled their DNA.

DNA is not loose inside a cell. It is packed and unpacked as needed, a bit like thread wound around spools. In this study, the force of a beating heart appeared to reshape that control system, pushing cancer cells away from a growth-friendly state.

In rare human heart metastases, the researchers saw signs that this DNA packaging had changed. The tumors had a shared pattern, even though they came from different kinds of cancer. They also showed changes in chemical marks that help control whether growth genes stay quiet or become active.

The message was clear: the beating heart was not just pushing on cancer cells from the outside. It appeared to change the way those cells controlled their genes.

“What’s really striking is this link they provide between mechanical load and epigenetic regulation,” Javid Moslehi, a cardiologist at the University of California, San Francisco who was not involved in the study, also told STAT. “They show that these physical forces can directly alter gene expression in cancer cells, which is a powerful concept that extends beyond cardiology.”

Removing the Break

To test whether Nesprin-2 truly mattered in this case, the researchers silenced it in lung cancer cells before implanting those cells into mouse hearts.

The result cut to the heart of the experiment (pun intended). Without Nesprin-2, cancer cells regained the ability to grow even in the presence of normal mechanical load. They formed large tumors in beating hearts that would otherwise have resisted them.

That finding suggests that the heart does not simply crush tumors by motion alone. Its mechanical force seems to activate a molecular brake inside cancer cells. Disable the brake, and the cancer cells proliferate in the environment where they would normally stay away from.

“Our findings show that the heart’s pulsation is not merely a physiological function but may act as a natural suppressor of tumor growth,” Zacchigna said in a statement. “This suggests that the cardiac environment is unfavorable to cancer cells not only for immunological or metabolic reasons, but also because its continuous mechanical activity physically constrains their expansion.”

Could Tumors Be Treated With Motion?

Much of the work took place in mice, transplanted hearts and engineered tissues. However, human cancers grow in more complex environments, surrounded by immune cells, different blood vessels, scar tissue, and chemical signals.

Still, the findings have already pushed the authors toward a provocative experiment: applying rhythmic mechanical stimulation to tumors outside the heart.

Zacchigna’s team has partnered with engineers to develop devices that could sit on the skin and apply pressure to tumors closer to the surface, such as some skin or breast cancers.

“We have the first prototypes, and results are promising,” Zacchigna told STAT. “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.”

Such an approach would need extensive testing. Researchers would have to learn which tumors respond to force, how much pressure to apply, how often to apply it, and whether mechanical stimulation could ever have unwanted effects. Cancer cells differ widely, and a force that restrains one tumor type might do little to another.

For now, the discovery adds another layer to how scientists understand the heart. Its constant motion may also help shape how cells behave. In the heart, that motion appears to make life harder for cancer.

The findings appeared in the journal Science.