Metastasis-on-a-Chip Program Illustrates How Tumors Spread

New system could lead to advances in cancer investigation and drug discovery.

The development of a new mini model shows how tumors spread and respond to treatment, paving the way for future individualized patient care.

The “metastasis-on-a-chip” system is among the first laboratory models that show cancer spreading from one 3D tissue to another.

Although the original version model showed colorectal tumors that spread from the colon to the liver, future system models will include additional organs like lung and bone marrow that are also potential sites for metastasis. Furthermore, researchers hope to model other cancers like glioblastoma.

“We believe the metastasis-on-a-chip system has potential for making meaningful advances in cancer investigation and drug discovery,” said lead study author Aleks Skardal, PhD.

A study published in Biotechnology and Bioengineering showed how the system encapsulates human intestine and colorectal cancer cells inside a biocompatible gel-like material that creates a mini organ and mini liver.

Next, researchers placed the organs in a chip system that consisted of a set of micro-channels and chambers etched in the chip’s surface that mimics a more simplified version of the circulatory system.

The tumor cells were tagged with fluorescent molecules, so that researchers could view cellular activity under a microscope.

The results of the study showed that the highly aggressive cancer cells in the colon organoid caused the tumor to grow until the cells were able to break free. The cells entered into the circulatory system and invaded the liver tissue where an additional tumor was formed.

The less aggressive cancer cells used in the system caused the tumor to not metastasize, but it did continue to grow in the colon, however.

Researchers wanted to test the system with the screening drug Marimastat, which is used to inhibit metastasis. When Marimastat was introduced into the system, there was significant prevention in the migration of metastatic cells over 10 days.

When the colorectal cancer drug 5-fluorouracil was tested, it resulted in the reduction of metabolic activity in tumor cells.

“We are currently exploring whether other established anti-cancer drugs have the same effects in the system as they do in patients,” Skardal said. “If this link can be validated and expanded, we believe the system can be used to screen drug candidates for patients as a tool in personalized medicine. If we can create the same model systems, only with tumor cells from an actual patient, then we believe we can use this platform to determine the best therapy for any individual patient.”

This system opens the doors to study the microenvironment of the tumor and address some of the shortcomings in current research methods.

In order to refine the new system, researchers plan to use 3D printing to create organoids that are similar in function to natural organs and as realistic as possible.

Additionally, researchers plan to add a barrier of endothelial cells to the model in order to block tumor cells from breaking through blood vessels and entering into the blood stream.