New Human Organ Chip Shows Exactly How Cancer Spreads to Bone and Lung

Most cancer deaths are not caused by the original tumor but by cells that break away, travel through the bloodstream, and form new tumors in distant organs — a process called metastasis, responsible for at least two-thirds of cancer deaths. Despite decades of research, drugs aimed at stopping metastasis have had limited success, partly because rodent biology cannot fully reproduce what happens in human patients. Researchers at Columbia Engineering, led by professor Gordana Vunjak-Novakovic, have now built a multi-organ chip that recreates this process using human tissue. The study was published in Science Translational Medicine.

The chip contains separate compartments of millimeter-scale bone and lung tissue connected by a flowing vascular channel, letting researchers watch circulating breast cancer cells attach to the blood vessel lining, cross it, and colonize the tissue beyond — a stage of metastasis called organ colonization that is very hard to observe directly in patients. The team built the bone, lung and blood vessel lining from induced pluripotent stem cells, which can be guided to grow into many specialized cell types.

Cancer cells that typically spread to bone colonized the engineered bone more strongly and caused more extensive damage there, while cells with an affinity for lung caused greater damage in the lung tissue while only modestly colonizing bone — matching known patterns of organ tropism, in which particular cancers favor particular organs. “Cancer is very smart, unfortunately. We learned how the cells cross barriers to get from blood circulation into the tissues,” Vunjak-Novakovic said.

The chip also showed that breast cancer cells release signals that alter a distant organ's environment before they even arrive, a process called pre-metastatic niche formation. Vunjak-Novakovic said the model's key advantage is that it is human and can be made patient-specific, letting researchers alter one component at a time to search for molecular pathways that could become new treatment targets.