University of Toronto's MInD organ-on-a-chip: breast cancer cells invade heart tissue less than liver

Researchers at the University of Toronto, with Professor Milica Radisic as senior author, describe in Nature Communications on nature.com a multi-organ-on-a-chip device called the Multi-organ Invasion Device (MInD). It was built to study why the ventricular myocardium is one of the least common sites of metastasis nature.comnature.comnature.comOpen source ↗. In the device, highly aggressive breast cancer cells invaded engineered cardiac tissue significantly less than hepatic tissue. All experiments were carried out in vitro on engineered tissues.

Metastasis is responsible for over 90% of cancer-related deaths. Resistance of the heart to metastatic colonization has been observed across various cancer types, yet it remains one of the least explored areas in cancer research. The authors note that animal models differ from humans in gene expression, immune system, metabolism and tumor kinetics, while 2D cultures do not reproduce tissue architecture and biochemical gradients.

How the MInD platform works

MInD is an open-well plate platform in which several organ compartments are cultured under flow. The compartments are connected by PermeoTubes, 3D-printed porous conduits that support cancer cell intravasation, migration and extravasation. Each is an extrusion-printed viscoelastic conduit made from granular polymeric ink, designed for multi-scale porosity, permeability and physiologically relevant mechanical stability. According to the university's summary, it is made from a biodegradable elastic polymer.

In the experiments, a central compartment with breast cancer cells was connected to a cardiac compartment or to a hepatic one. The liver, a common site of breast cancer metastasis, served as the control nature.comnature.comnature.comOpen source ↗.

What the co-cultures showed

In dual-organ devices, invasion into cardiac tissue was significantly suppressed relative to hepatic co-culture. In cardiac–hepatic–cancer tri-culture, the presence of cardiac tissue reduced overall invasion, and cancer cells preferentially migrated toward the hepatic compartments.

Cytokine profiling and RNA sequencing showed that cardiac co-culture suppressed cell metastasis and invasion while inducing immune activation. Compared with hepatic co-culture, pro-metastatic and immunosuppressive cytokines were broadly downregulated. Immune-activating signals, antigen-presentation pathways via MHC class II and pro-apoptotic gene programs were upregulated.

The authors say the platform offers an approach for identifying organ-specific drivers of metastasis and could speed up the discovery of metastasis-inhibiting therapies nature.comnature.comnature.comOpen source ↗.