The heart's hidden shield against cancer

Cancer can spread throughout the body, yet it rarely takes hold in the heart. This unusual resistance has long puzzled scientists and may contain important clues for preventing metastasis in other organs.

Researchers at the University of Toronto have now developed a multi-organ-on-a-chip platform that makes it possible to study this phenomenon in a controlled laboratory setting. Using the platform, the team found that aggressive breast cancer cells readily invaded engineered liver tissue but showed significantly reduced invasion into cardiac tissue.

Published in Nature Communications, the platform, called the Multi-organ Invasion Device (MInD), connects multiple engineered tissues within a single system under dynamic fluid flow. It allows researchers to observe how cancer cells move between tissue environments and how each organ influences their behaviour.

"The goal was to create a platform that captures key steps of the metastatic process while allowing us to observe interactions between different tissues under controlled conditions," says Milica Radisic, professor in the Institute of Biomedical Engineering and the Department of Chemical Engineering and Applied Chemistry at the University of Toronto and senior author of the study. "Current models have important limitations, either because they cannot reproduce the complexity of human tissues or because they do not have a good way to connect organ compartments via a common circulation. MInD provides a new way to investigate these interactions."

Metastasis is responsible for more than 90 per cent of cancer-related deaths, but the biological processes that determine where tumour cells spread remain difficult to study. Traditional cell cultures lack the complexity of living tissues, while animal models make it challenging to isolate the effects of individual organs and their microenvironments.

To address these challenges, the researchers engineered MInD as an open-well, multi-organ platform in which different tissues can be cultured simultaneously. The team also developed a new method for manufacturing the PermeoTubes using a biodegradable elastic polymer and granular 3D-printing techniques. The tubes contain interconnected pores that support cancer cell migration and biochemical communication between tissues while maintaining mechanical properties similar to those found in native biological structures.

The researchers used the platform to compare two very different destinations for metastatic breast cancer cells: engineered cardiac tissue and liver tissue, a common site of breast cancer metastasis. In devices containing either tissue, cancer cells migrated readily toward the liver but showed significantly less invasion into the cardiac tissue.

The difference was even clearer when cardiac tissue, liver tissue and cancer cells were cultured together in the same device. Cancer cells preferentially migrated toward the liver compartment, while the presence of cardiac tissue reduced overall invasion.

The findings demonstrated that the platform could reproduce organ-specific differences in metastatic behaviour while providing researchers with detailed insight into the biological signals involved. Analysis of proteins and gene expression revealed that cardiac tissue altered pathways associated with metastasis, immune responses and cell migration, supressing metastasis to the heart.

“We were able to monitor where cancer cells moved in real time and see how different tissue environments influenced their behaviour at the molecular level,” says Amid Shakeri, the study’s first author. “MInD gives us a new way to investigate why some tissues resist metastasis while others are more permissive, and it may help identify strategies to limit cancer spread elsewhere in the body.”

Beyond cancer research, the team believes the underlying manufacturing approach may also have applications in the broader organ-on-a-chip field, where researchers seek to recreate human physiology in vitro for drug testing and disease modelling.