Researchers at Columbia University have developed a human multi organ chip that mimics how breast cancer cells travel through the bloodstream and spread to distant organs. The platform combines engineered human bone and lung tissue with vascular circulation, allowing researchers to study important stages of metastasis in a controlled laboratory environment.
The study addresses a major challenge in cancer research. Metastasis is responsible for at least two thirds of cancer deaths, while drugs aimed at stopping metastatic progression have largely failed. Animal models have contributed significantly to understanding cancer, but biological differences between animals and humans can limit how accurately these models predict processes in patients. The new platform is designed to complement existing research methods with a model based on human cells and tissues.
Recreating metastasis in human tissue
The multi organ chip was developed by a team led by Gordana Vunjak Novakovic, professor of biomedical engineering and medical sciences at Columbia University. Her laboratory has extensive experience developing microphysiological systems, also known as organs on a chip. For this model, researchers created millimeter sized human bone and lung tissues, two common sites for breast cancer metastases. The tissues and the vascular endothelium, the cellular lining of blood vessels, were engineered using induced pluripotent stem cells.
Bone and lung tissues are maintained in separate compartments, each optimized to preserve tissue functionality. The compartments are connected through vascular circulation. A selectively permeable endothelial barrier separates the bloodstream from the tissues, similar to the situation in the human body. The researchers introduced circulating human breast cancer cells into the vascular system and observed how they interacted with the endothelium, crossed the vascular barrier and entered the different tissues.
The chip reproduced important patterns seen in patients. Breast cancer cells known to favor bone showed stronger colonization of the engineered bone tissue and caused more pronounced bone degeneration. Cancer cells with a preference for the lungs caused greater disruption of lung tissue and only limited colonization of bone. These differences suggest that the model can reproduce important elements of organ specific metastasis.
Studying organ colonization
One of the main advantages of the technology is its ability to study organ colonization. After cancer cells leave a primary tumor and enter the bloodstream, only some succeed in reaching another organ, crossing the blood vessel wall and surviving there. To establish a new tumor, these cells must adapt to their environment and influence surrounding tissue. Such processes are difficult to investigate directly in patients. The chip gives scientists an opportunity to examine these interactions using human cells and tissues while controlling individual components of the system.
The experiments also revealed changes occurring before cancer cells actually colonized an organ. Researchers found evidence of pre metastatic niche formation, a process in which cancer influences distant tissues and makes them more receptive to future colonization.
According to Vunjak Novakovic, the model reproduced the phenomenon seen in patients whereby cancer cells effectively prepare target tissues before establishing metastases. This could help researchers investigate the molecular signals involved and potentially identify new therapeutic targets.
New platform
The researchers see the technology primarily as a new platform for preclinical cancer research. Because specific elements of the system can be manipulated, scientists can study interactions between tumor cells, blood vessels and individual organ environments in greater detail. Another potential advantage is personalization. The platform is based on engineered human tissues and could eventually incorporate cells derived from individual patients. This may provide researchers with a way to investigate why particular cancers are more likely to spread to certain organs or how metastatic disease responds to potential treatments.
The approach also reflects growing interest in human based experimental models that can complement animal research. According to the researchers, such systems could provide information about human disease mechanisms that is difficult to obtain with conventional methods. Further development and validation are required before the technology can be used for drug development or personalized treatment decisions. The study nevertheless shows that a multi organ chip can reproduce several crucial aspects of breast cancer metastasis, including vascular circulation, invasion of tissue, organ specific colonization and preparation of distant organs for cancer spread.
By making these processes observable in human engineered tissues, the platform could provide a valuable new tool for understanding why breast cancer spreads and for developing treatments aimed at preventing metastasis.
References
Science Translational Medicine (research)
