Published in Science: an international study reveals how mechanical forces in cardiac tissue inhibit cancer cell proliferation
The rhythmic beating of the heart may play an unexpected role in protecting it from cancer. An international study, published in Science and coordinated by the Cardiovascular Biology laboratory of the International Centre for Genetic Engineering and Biotechnology (ICGEB) in collaboration with the University of Trieste, demonstrates that the mechanical forces generated by cardiac contraction can significantly slow tumour growth in both mouse and human hearts.
The study, entitled “Mechanical load inhibits tumour growth in mouse and human hearts”, highlights a mechanism that has remained largely unexplored: the physical forces acting on the myocardium not only regulate cardiac function but also directly influence the behaviour of tumour cells, limiting their proliferation.
The research brought together a broad European network of institutions, including the Medical University of Innsbruck, King’s College London, University Medical Centre Hamburg-Eppendorf, Simula Research Laboratory in Oslo, IEO and Centro Cardiologico Monzino, ICGEB and the University of Trieste. This collaboration enabled the combination of experimental biology, clinical investigation, bioengineering and computational modelling.
A long-standing clinical observation provided the starting point for the study: primary tumours of the heart are extremely rare, and even metastatic lesions in cardiac tissue are typically smaller than those found in other organs. While this phenomenon is well known in medicine, its underlying mechanisms have remained unclear.
Researchers hypothesised that the answer might lie in the unique mechanical environment of the heart, a tissue constantly subjected to contraction, pressure and deformation. To test this, the team, headed by Prof. Serena Zacchigna, employed innovative experimental models.
In mouse models, scientists examined what happens when the heart is mechanically “unloaded.” Under reduced mechanical stress, tumour cells proliferated significantly more. In parallel, engineered cardiac tissues developed in the laboratory allowed precise modulation of mechanical load. Across all systems analysed, the findings were consistent: when cardiac tissue beats and generates mechanical load, tumour growth slows; when this mechanical stimulus is reduced, cancer cells resume proliferation.
Crucially, the study reveals that the impact of mechanical forces extends beyond the cell surface. The researchers demonstrated that cardiac mechanical load influences internal molecular mechanisms that regulate tumour cell division. This establishes a direct link between the mechanical properties of the cellular microenvironment and epigenetic regulation within cancer cells.
“Our findings show that the heart’s pulsation is not merely a physiological function but may act as a natural suppressor of tumour growth,” said Prof. Zacchigna. “This suggests that the cardiac environment is unfavourable to cancer cells not only for immunological or metabolic reasons, but also because its continuous mechanical activity physically constrains their expansion.”
Prof. Giulio Pompilio, MD, Scientific Director of the Monzino Cardiological Centre IRCCS, added, “This work was made possible thanks to the collaboration of experts from various fields, ranging from cardiology and oncology to bioengineering and bioinformatics”.
An important strength of the study lies in its translational dimension. Results obtained in experimental systems were compared with human cardiac metastases and analysed alongside lesions located in other organs from the same patients. The distinct biological patterns observed in laboratory models were confirmed in human samples, reinforcing the robustness and clinical relevance of the findings.
Although the research does not propose an immediate therapeutic application, it opens an entirely new avenue of investigation as to whether mechanical stimuli could, in the future, be harnessed as a therapeutic strategy against cancer. The concept of a “mechanical therapy” remains to be developed, but the principle emerging from this work is clear – physical forces are not merely a passive context for disease; they can act as regulators of tumour growth.
A deeper understanding of how cancer cells respond to pressure, movement and mechanical load could shed light on tumour behaviour in other organs and potentially inspire new therapeutic strategies that target not only molecular pathways but also the physical characteristics of tissues.
In an increasingly interdisciplinary scientific landscape, this study exemplifies the power of integrating advanced experimentation, human sample analysis, computational modelling and international collaboration to uncover previously unrecognised dimensions of disease biology.
Link to article: Mechanical load inhibits tumour growth in mouse and human hearts
