Cytokine Profiling and RNA Sequencing Reveal Immune Activation and Metastatic Suppression in Cardiac Microenvironments

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Summary of  Nature Communications  https://doi.org/10.1038/s41467-026-75833-9 
Dr. Amid Shakeri et al.

Points

University of Toronto researchers developed a multi organ on a chip platform to examine why the ventricular myocardium resists cancer metastasis compared to permissive sites like the liver.
The device connected organ compartments using porous three dimensionally printed polymer conduits that supported dynamic fluid flow and real time cancer cell migration analysis.
Co culture assays revealed that aggressive breast cancer cell invasion into engineered cardiac tissue was significantly suppressed compared to parallel liver tissue co culture models.
Tri culture experiments combining cardiac and hepatic tissues confirmed that the presence of cardiac tissue reduced overall metastasis while directing cell migration toward hepatic compartments.
Authors concluded that cardiac tissue alters gene expression and cytokine signaling to inhibit metastasis offering a novel platform for developing anti metastatic therapeutics.

Summary

This study evaluated the mechanisms underlying cardiac resistance to metastatic invasion using an engineered multi-organ-on-a-chip platform. Published in Nature Communications by University of Toronto researchers led by senior author Milica Radisic and first author Amid Shakeri, the investigation addressed the long-standing clinical observation that the ventricular myocardium remains one of the least common anatomical sites for cancer metastasis, despite accounting for over 90% of cancer-related mortality worldwide. Given that traditional 2D cell cultures and animal models fail to isolate organ-specific microenvironmental factors, the research sought to model dynamic cancer cell intravasation, migration, and extravasation under controlled microfluidic flow.

The microfluidic system, designated the Multi-organ Invasion Device (MInD), incorporated open-well organ compartments interconnected by PermeoTubes—3D-printed porous conduits manufactured from biodegradable elastic polymers. In dual-organ co-culture assays, highly aggressive metastatic breast cancer cells demonstrated significantly suppressed invasion into engineered cardiac tissue relative to hepatic co-cultures. Furthermore, in cardiac–hepatic–cancer tri-culture experiments, the inclusion of cardiac tissue reduced overall systemic cancer cell invasion, with metastatic cells preferentially migrating toward the hepatic compartment. Cytokine profiling and RNA sequencing revealed that cardiac co-culture downregulated metastatic and cell-migration signaling pathways while upregulating immune activation pathways within the microenvironment.

The authors conclude that engineered cardiac tissue exerts active biochemical and immunomodulatory resistance against cancer cell invasion. By successfully recapitulating organ-specific metastatic tropes in vitro, the MInD platform provides a robust model for uncovering protective organ microenvironments and accelerating the development of metastasis-inhibiting therapeutics.

Link to the article: https://www.nature.com/articles/s41467-026-75833-9

References

Shakeri, A., Abdo, D., Lei, M. H. C., Okhovatian, S., Beeghly, G. F., Popovic, A. M., Jiang, R., Liu, C., Wagner, K. T., Vosoughi, D., Kieda, J., Fish, J. E., & Radisic, M. (2026). In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis. Nature Communications, 17(1), 8920. https://doi.org/10.1038/s41467-026-75833-9