The heart’s constant beating may actively suppress tumor growth in cardiac tissues, a new study reports. This is because cellular pathways in these tissues alter gene regulation in cancer cells to keep them from proliferating. The findings shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to new cancer therapies based on mechanical stimulation. Heart cancer is very rare in mammals. What’s more, the adult human heart has a limited capacity for self-renewal, with cardiomyocytes regenerating at roughly 1% per year. One proposed explanation for these features lies in the intense mechanical demands placed on heart tissues, which must continuously pump blood against significant resistance. Such persistent strain appears to suppress the ability of heart cells to proliferate. According to Giulio Ciucci and colleagues, these pressures may also inhibit the proliferation of cancer cells in the heart. However, the mechanisms underlying this resistance remain unclear.

 

Using a genetically engineered mouse model, Ciucci et al. found that the heart is remarkably resistant to cancer-causing mutations, even when potent oncogenic changes were introduced. To understand why, the authors developed a transplantation model in which the heart’s mechanical workload could be reduced. By grafting a donor heart into the neck of a compatible mouse, they created a “mechanically unloaded” organ, one that remained perfused with blood but did not bear physiological strain. After injecting human cancer cells directly into the heart muscle, they compared tumor behavior in the unloaded transplanted heart versus the animal’s native, mechanically active heart. Across their experiments, Ciucci et al. found that mechanical load consistently suppressed the growth of various cancer types, while unloading the heart promoted tumor cell proliferation within cardiac tissue. According to the findings, mechanical forces within the tissue reshape the cancer cell genome’s regulatory landscape, influencing whether cells can proliferate. Central to this process is Nesprin-2, a protein that transmits mechanical signals from the cell surface to the nucleus. Nesprin-2, a component of the LINC complex, senses the mechanical microenvironment of the heart and functionally alters chromatin structure and histone methylation, reducing gene activity linked to tumor cell proliferation. When Nesprin-2 was silenced in cancer cells, those cells regained the ability to grow in the mechanically active environment of the heart, forming tumors. In a related Perspective, Wyatt Paltzer and James Martin discuss the study and its findings in greater detail.

 

For reporters interested in topics of research integrity, study co-author Serena Zacchigna notes: “We are working to ensure reproducibility of complex mechanobiology experiments, standardizing mechanical stimulation protocols, and validating results across models and labs. I also believe that data reporting is essential, as is rigorous assessment of safety and efficacy. Ethically, as a medical doctor, I believe that early patient involvement in the design of wearable technologies is a priority, avoiding overstated claims.”

 

Podcast: A segment of Science's weekly podcast with Giulio Ciucci, related to this research, will be available on the Science.org podcast landing page after the embargo lifts. Reporters are free to make use of the segments for broadcast purposes and/or quote from them – with appropriate attribution (i.e., cite "Science podcast"). Please note that the file itself should not be posted to any other Web site.

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